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Giovanni GUARALDI

Professore Ordinario
Dipartimento Chirurgico, Medico, Odontoiatrico e di Scienze Morfologiche con interesse Trapiantologico, Oncologico e di Medicina Rigenerativa

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Pubblicazioni

2024 - Ageism: the -ism affecting the lives of older people living with HIV [Articolo su rivista]
Guaraldi, Giovanni; Milic, Jovana; Cascio, Mario; Mussini, Cristina; Martinez, Esteban; Levin, Jules; Calzavara, Daniele; Mbewe, Rebecca; Falutz, Julian; Orkin, Chloe; Cesari, Matteo; Lazarus, Jeffrey V
abstract

: WHO defines ageism as stereotypes, prejudice, and discrimination based on age. Ageism is a multidimensional concept that encompasses multiple components related to the individual, the social group, and the institution in different cultural and environmental settings. In people ageing with HIV these elements include self-stigma, discrimination in society, and experiences in care, many of which are unique to older people. In this Position Paper, we use experience of people with HIV and clinicians taking care of them to explore these issues in high-income countries. The intersectionality of multiple -isms, which affect the lives of older people living with HIV, and ageism enhance several HIV-related issues, including self-inflicted stigma, and loneliness. Research is needed to explore how ageism contributes to worse physical, mental, and social wellbeing outcomes for people with HIV. The model of care for older people living with HIV needs to go beyond virological success by adopting a geriatric mindset, which is attentive to the challenge of ageism and is proactive in promoting a comprehensive approach for the ageing population. All stakeholders and the community should work together to co-create institutional strategies and educational programmes and enable respectful intergenerational dialogue to foster a stigma-free future for older people living with HIV.

2024 - Cardiometabolic health in people with HIV: expert consensus review [Articolo su rivista]
Batterham, Rachel L; Bedimo, Roger J; Diaz, Ricardo S; Guaraldi, Giovanni; Lo, Janet; Martínez, Esteban; Mccomsey, Grace A; Milinkovic, Ana; Naito, Toshio; Noe, Sebastian; O’Shea, Donal; Paredes, Roger; Schapiro, Jonathan M; Sulkowski, Mark S; Venter, François; Waters, Laura; Yoruk, Ilksen Ungan; Young, Benjamin
abstract

Objectives To develop consensus data statements and clinical recommendations to provide guidance for improving cardiometabolic health outcomes in people with HIV based on the knowledge and experience of an international panel of experts.Methods A targeted literature review including 281 conference presentations, peer-reviewed articles, and background references on cardiometabolic health in adults with HIV published between January 2016 and April 2022 was conducted and used to develop draft consensus data statements. Using a modified Delphi method, an international panel of 16 experts convened in workshops and completed surveys to refine consensus data statements and generate clinical recommendations.Results Overall, 10 data statements, five data gaps and 14 clinical recommendations achieved consensus. In the data statements, the panel describes increased risk of cardiometabolic health concerns in people with HIV compared with the general population, known risk factors, and the potential impact of antiretroviral therapy. The panel also identified data gaps to inform future research in people with HIV. Finally, in the clinical recommendations, the panel emphasizes the need for a holistic approach to comprehensive care that includes regular assessment of cardiometabolic health, access to cardiometabolic health services, counselling on potential changes in weight after initiating or switching antiretroviral therapy and encouraging a healthy lifestyle to lower cardiometabolic health risk.Conclusions On the basis of available data and expert consensus, an international panel developed clinical recommendations to address the increased risk of cardiometabolic disorders in people with HIV to ensure appropriate cardiometabolic health management for this population.

2024 - Development and validation of a prediction score for failure to casirivimab/imdevimab in hospitalized patients with COVID-19 pneumonia [Articolo su rivista]
Cozzi-Lepri, Alessandro; Borghi, Vanni; Rotundo, Salvatore; Mariani, Bianca; Ferrari, Anna; Del Borgo, Cosmo; Bai, Francesca; Colletti, Pietro; Miraglia, Piermauro; Torti, Carlo; Cattelan, Anna Maria; Cenderello, Giovanni; Berruti, Marco; Tascini, Carlo; Parruti, Giustino; Coladonato, Simona; Gori, Andrea; Marchetti, Giulia; Lichtner, Miriam; Coppola, Luigi; Sorace, Chiara; D'Abramo, Alessandra; Mazzotta, Valentina; Guaraldi, Giovanni; Franceschini, Erica; Meschiari, Marianna; Sarmati, Loredana; Antinori, Andrea; Nicastri, Emanuele; Mussini, Cristina
abstract

Introduction Casirivimab and imdevimab (CAS/IMV) are two non-competing, high-affinity human IgG1 anti-SARS-CoV-2 monoclonal antibodies, that showed a survival benefit in seronegative hospitalized patients with COVID-19. This study aimed to estimate the day-28 risk of mechanical ventilation (MV) and death in individuals hospitalized for severe COVID-19 pneumonia and receiving CAS/IMV. Additionally, it aimed to identify variables measured at the time of hospital admission that could predict these outcomes and derive a prediction algorithm.Methods This is a retrospective, observational cohort study conducted in 12 hospitals in Italy. Adult patients who were consecutively hospitalized from November 2021 to February 2022 receiving CAS/IMV were included. A multivariable logistic regression model was used to identify predictors of MV or death by day 28 from treatment initiation, and beta-coefficients from the model were used to develop a risk score that was derived by means of leave-one-out internal cross-validation (CV), external CV, and calibration. Secondary outcome was mortality.Results A total of 480 hospitalized patients in the training set and 157 patients in the test set were included. By day 28, 36 participants (8%) underwent MV and 28 died (6%) for a total of 58 participants (12%) experiencing the composite primary endpoint. In multivariable analysis, four factors [age, PaO2/FiO2 ratio, lactate dehydrogenase (LDH), and platelets] were independently associated with the risk of MV/death and were used to generate the proposed risk score. The accuracy of the score in the area under the curve (AUC) was 0.80 and 0.77 in internal validation and test for the composite endpoint and 0.87 and 0.86 for death, respectively. The model also appeared to be well calibrated with the raw data.Conclusion The mortality risk reported in our study was lower than that previously reported. Although CAS/IMV is no longer used, our score might help in identifying which patients are not likely to benefit from monoclonal antibodies and may require alternative interventions.

2024 - Inclusive healthcare in light of the new MASLD guidelines: Should people living with HIV be screened for liver fibrosis? [Articolo su rivista]
Sebastiani, Giada; Cinque, Felice; Cascio, Antonio; Rockstroh, Jürgen K.; Guaraldi, Giovanni
abstract

2024 - Metabolic dysfunction‐associated steatohepatitis exhibits sex differences in people with HIV [Articolo su rivista]
Kablawi, Dana; Milic, Jovana; Thomas, Tyler; Fotsing Tadjo, Thierry; Cinque, Felice; Elgretli, Wesal; Gioè, Claudia; Lebouché, Bertrand; Tsochatzis, Emmanuel; Finkel, Jemima; Bhagani, Sanjay; Cascio, Antonio; Guaraldi, Giovanni; Mazzola, Giovanni; Saeed, Sahar; Sebastiani, Giada
abstract

Objectives People with HIV are at increased risk for metabolic dysfunction-associated steatohepatitis (MASH). Although sex differences are documented in the general population, their role in the context of HIV is less understood. Methods This was a multicentre cohort study including people with HIV without viral hepatitis coinfection. A FibroScan-AST (FAST) score >0.35 was used to diagnose MASH with significant liver fibrosis (stage F2-F4). We investigated sex-based differences in MASH trends as a function of age using a segmented linear mixed-effects model. Random effects accounted for clustering by the four sites. Adjusted models included ethnicity, diabetes, hypertension, and detectable HIV viral load. Results We included 1472 people with HIV (25% women). At baseline, the prevalence of MASH with fibrosis by FAST score was lower in women than in men (4.8% vs. 9.2%, p = 0.008). Based on the adjusted model, male sex (+0.034; p = 0.04), age per year (+0.003; p = 0.05), detectable HIV viral load (+0.034; p = 0.02), and hypertension (+0.03; p = 0.01) were positively associated with MASH with fibrosis. Although men exhibited generally higher FAST scores, FAST scores increased in women during the critical biological age of presumed perimenopause to menopause (between 40 and 50 years), reaching levels similar to those in men by the age of 55 years. Conclusion Despite women with HIV having a lower prevalence of MASH with fibrosis than men, they exhibit an acceleration in FAST score increase around the perimenopausal age. Future studies should target adequate consideration of sex differences in clinical investigation of metabolic dysfunction-associated steatotic liver disease to fill current gaps and implement precision medicine for people with HIV.

2024 - Metabolic dysfunction-associated steatotic liver disease: An opportunity for collaboration between cardiology and hepatology [Articolo su rivista]
Raggi, Paolo; Milic, Jovana; Manicardi, Marcella; Cinque, Felice; Swain, Mark G.; Sebastiani, Giada; Guaraldi, Giovanni
abstract

: Altered metabolic function has many detrimental effects on the body that can manifest as cardiovascular and liver diseases. Traditional approaches to understanding and treating metabolic dysfunction-associated disorders have been organ-centered, leading to silo-type disease care. However, given the broad impact that systemic metabolic dysfunction has on the human body, approaches that simultaneously involve multiple medical specialists need to be developed and encouraged to optimize patient outcomes. In this review, we highlight how several of the treatments developed for cardiac care may have a beneficial effect on the liver and vice versa, suggesting that there is a need to target the disease process, rather than specifically target the cardiovascular or liver specific sequelae of metabolic dysfunction.

2024 - Non-AIDS-defining comorbidities impact health related quality of life among older adults living with HIV [Articolo su rivista]
Zhabokritsky, Alice; Klein, Marina; Loutfy, Mona; Guaraldi, Giovanni; Andany, Nisha; Guillemi, Silvia; Falutz, Julian; Arbess, Gordon; Tan, Darrell H. S.; Walmsley, Sharon
abstract

Introduction The life expectancy of people living with HIV receiving effective combination antiretroviral therapy is approaching that of the general population and non AIDS-defining age-related comorbidities are becoming of greater concern. In order to support healthy aging of this population, we set out to explore the association between multimorbidity (defined as presence of 2 or more non AIDS-defining comorbidities) and quality of life (QoL).Methods We performed a cross-sectional analysis using data from the Correlates of Healthy Aging in Geriatric HIV (CHANGE HIV) study, a Canadian cohort of people living with HIV age 65 years and older. Study participants completed two QoL modules, the general QoL and health related QoL (HR-QoL).Results 433 participants were included in the analysis with a median age of 69 years (interquartile range, IQR 67-72). The median number of comorbidities among study participants was 3 (IQR 2-4), with 78% meeting the definition of multimorbidity. General QoL scores (median 66, IQR 58-76) were lower than HR-QoL scores (median 71, IQR 61-83) and were not associated with multimorbidity after adjusting for age, sex, relationship status, household income, exercise, tobacco smoking history, malnutrition, time since HIV diagnosis, and HIV-related stigma. In contrast, multimorbidity was associated with lower HR-QoL (adjusted beta = -4.57, 95% CI -8.86, -0.28) after accounting for the same variables. Several social vulnerabilities (not having a partner, low household income), health behaviours (lower engagement in exercise, smoking), and HIV-related factors (HIV stigma, longer time since HIV diagnosis) were also associated with lower QoL.Discussion Overall, our study demonstrated a high burden of multimorbidity among older adults living with HIV in Canada, which has a negative impact on HR-QoL. Interventions aimed at preventing and managing non-AIDS-defining comorbidities should be assessed in people living with HIV to determine whether this can improve their HR-QoL.

2024 - Optimizing the antiretroviral treatment focusing on long-term effectiveness and a person-centered approach. Consensus Guidance Using a Delphi Process [Articolo su rivista]
Maggiolo, F; Lo Caputo, S; Bonora, S; Borderi, M; Cingolani, A; D'Ettorre, G; Di Biagio, A; Di Giambenedetto, S; Gervasoni, C; Guaraldi, G; Maggi, P; Taramasso, L.
abstract

: Definitive data on the long-term success of the latest antiretroviral therapy (ART) strategies are still lacking. A panel of infectious diseases specialists was convened to develop a consensus on how to tailor and follow ART over time. Panelists used a Delphi technique to develop a list of statements describing preferred management approaches for ART and patient monitoring and quality of life evaluation. Ninety infectious diseases specialists from several Infectious Diseases Centers in Italy participated in the consensus process. A consensus was reached on virological and immunological parameters to use to monitor long-term efficacy of antiretroviral treatment, while there was no consensus on the use of specific inflammation and immune-activation markers in clinical routine. The panel agreed on the need for an antiretroviral treatment with the lowest impact on bone, kidney and cardiovascular toxicity and on the utility of quality-of-life monitoring during the standard follow up of people living with HIV. The consensus statements developed by a panel of infectious diseases specialists may provide guidance to practitioners for a person-centered approach aimed at obtaining long-term virological and clinical success for people living with HIV.

2024 - Sarcopenic obesity and reduced BMD in young men living with HIV: body composition and sex steroids interplay [Articolo su rivista]
De Vincentis, S.; Greco, C.; Fanelli, F.; Decaroli, M. C.; Diazzi, C.; Mezzullo, M.; Milic, J.; De Santis, M. C.; Roli, L.; Pagotto, U.; Guaraldi, G.; Rochira, V.
abstract

Purpose Sex steroids play a key role on male bone homeostasis and body composition (BC), their role in men living with HIV (MLWH) is less recognized. This study aimed at investigating the prevalence of low BMD, sarcopenia, and sarcopenic obesity (SO) and their relationship with sex steroids in MLWH aged < 50. Methods Prospective, cross-sectional, observational study on MLWH younger than 50 (median age 47.0 years). BC and BMD were evaluated with DXA. Two different definitions of sarcopenia were applied: appendicular lean mass/height(2) (ALMI) < 7.26 kg/m(2) or appendicular lean mass/body weight (ALM/W) < 28.27%. Low BMD was defined for Z-score < -2.0. Sarcopenia coupled with obesity identified SO. Serum total testosterone (T) and estradiol (E2) were measured by LC-MS/MS; free testosterone (cFT) was calculated by Vermeulen equation. Results Sarcopenia was detected in 107 (34.9%) and 44 (14.3%) out of 307 MLWH according to ALMI and ALM/W, respectively. The prevalence of SO was similar by using both ALMI (11.4%) and ALM/W (12.4%). Sarcopenic and SO MLWH had lower total T and cFT in both the definition for sarcopenia. BMD was reduced in 43/307 (14.0%). Serum E2 < 18 pg/mL was an independent contributing factor for sarcopenia, SO, and low BMD. Conclusions T and E2 are important determinants of BC even in MLWH. This is among the first studies investigating the distribution of obesity phenotypes and the prevalence of SO among MLWH showing that SO is present in 11-12% of enrolled MLWH regardless of the definition used. However, deep differences emerged using two different diagnostic definitions.

2024 - SARS‐CoV‐2 testing, positivity, and factors associated with COVID‐19 among people with HIV across Europe in the multinational EuroSIDA cohort [Articolo su rivista]
Fursa, O.; Bannister, W.; Neesgaard, B.; Podlekareva, D.; Kowalska, J.; Benfield, T.; Gerstoft, J.; Reekie, J.; Rasmussen, L. D.; Aho, I.; Guaraldi, G.; Staub, T.; Miro, J. M.; Laporte, J. M.; Elbirt, D.; Trofimova, T.; Sedlacek, D.; Matulionyte, R.; Oprea, C.; Bernasconi, E.; Hadžiosmanović, V.; Mocroft, A.; Peters, L.; Null, Null
abstract

Background: Although people with HIV might be at risk of severe outcomes from infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2; coronavirus 2019 [COVID-19]), regional and temporal differences in SARS-CoV-2 testing in people with HIV across Europe have not been previously described. Methods: We described the proportions of testing, positive test results, and hospitalizations due to COVID-19 between 1 January 2020 and 31 December 2021 in the EuroSIDA cohort and the factors associated with being tested for SARS-CoV-2 and with ever testing positive. Results: Of 9012 participants, 2270 (25.2%, 95% confidence interval [CI] 24.3-26.1) had a SARS-CoV-2 polymerase chain reaction test during the study period (range: 38.3% in Northern to 14.6% in Central-Eastern Europe). People from Northern Europe, women, those aged <40 years, those with CD4 cell count <350 cells/mm3 , and those with previous cardiovascular disease or malignancy were significantly more likely to have been tested, as were people with HIV in 2021 compared with those in 2020. Overall, 390 people with HIV (4.3%, 95% CI 3.9-4.8) tested positive (range: 2.6% in Northern to 7.1% in Southern Europe), and the odds of testing positive were higher in all regions than in Northern Europe and in 2021 than in 2020. In total, 64 people with HIV (0.7%, 95% CI 0.6-0.9) were hospitalized, of whom 12 died. Compared with 2020, the odds of positive testing decreased in all regions in 2021, and the associations with cardiovascular disease, malignancy, and use of tenofovir disoproxil fumarate disappeared in 2021. Among study participants, 58.9% received a COVID-19 vaccine (range: 72.0% in Southern to 14.8% in Eastern Europe). Conclusions: We observed large heterogeneity in SARS-CoV-2 testing and positivity and a low proportion of hospital admissions and deaths across the regions of Europe.

2024 - Steatotic liver disease and HIV: an agenda for 2030 [Articolo su rivista]
Pericàs, Juan M; Arora, Anish K; Riebensahm, Carlotta; Jiménez-Masip, Alba; Ramírez Mena, Adrià; White, Trenton M; Dedes, Nikos; Guaraldi, Giovanni; Berzigotti, Annalisa; Wandeler, Gilles; Bansal, Meena B; Navarro, Jordi; Lazarus, Jeffrey V
abstract

People living with HIV are particularly susceptible to developing metabolic disorders, including metabolic dysfunction-associated steatotic liver disease and other forms of SLD. However, people living with HIV have been historically excluded from clinical trials and large cohort studies of SLD. Therefore, our understanding of the risk factors and natural history of SLD in this population is poor. Moreover, relevant knowledge gaps on the epidemiology and barriers for adequate health care, such as stigma, hamper adequate responses to the ongoing HIV and SLD syndemic. This Viewpoint provides a comprehensive perspective on how to tackle SLD in people living with HIV by examining the role of social determinants of health in the development of liver disease and metabolic syndrome comorbidities among this population, emphasising the importance of prioritising SLD management, summarising the most urgent needs in the field, and offering recommendations for advancing research to fill key data gaps and protect liver health of people living with HIV.

2024 - The best place for doravirine [Articolo su rivista]
Mussini, Cristina; Guaraldi, Giovanni
abstract

2024 - The effect of weight gain and metabolic dysfunction-associated steatotic liver disease on liver fibrosis progression and regression in people with HIV [Articolo su rivista]
Guaraldi, Giovanni; Milic, Jovana; Renzetti, Stefano; Motta, Federico; Cinque, Felice; Bischoff, Jenny; Desilani, Andrea; Conti, Jacopo; Medioli, Filippo; del Monte, Martina; Kablawi, Dana; Elgretli, Wesal; Calza, Stefano; Mussini, Cristina; Rockstroh, Juergen K.; Sebastiani, Giada
abstract

Objective: People with HIV (PWH) have high risk of liver fibrosis. We investigated the effect of weight gain and metabolic dysfunction-associated steatotic liver disease (MASLD) on liver fibrosis dynamics. Design: Multicenter cohort study. Methods: Fibrosis progression was defined as development of significant fibrosis (liver stiffness measurement [LSM]≥8 kPa), or transition to cirrhosis (LSM≥13 kPa), for those with significant fibrosis at baseline. Fibrosis regression was defined as transition to LSM<8 kPa, or to LSM<13 kPa for those with cirrhosis at baseline. MASLD was defined as hepatic steatosis (controlled attenuation parameter >248 dB/m) with at least one metabolic abnormality. A continuous-time multi-state Markov model was used to describe transitions across fibrosis states. Results: Among 1183 PWH included from three centres (25.2% with viral hepatitis coinfection), baseline prevalence of significant fibrosis and MASLD was 14.4% and 46.8%, respectively. During a median follow-up of 2.5 years (interquartile range 1.9-3.5) the incidence rate of fibrosis progression and regression was 2.8 (95% CI, 2.3-3.4) and 2.2 (95% CI, 1.9-2.6) per 100 person-years, respectively. In Markov model, weight gain increased the odds of fibrosis progression (odds ratio [OR] 3.11, 95% CI 1.59-6.08), whereas weight gain (OR 0.30, 95% CI 0.10-0.84) and male sex (OR 0.32, 95% CI 0.14-0.75) decreased the odds of fibrosis regression. On multivariable Cox regression analysis, predictors of fibrosis progression were weight gain (adjusted hazard ratio [aHR] 3.12, 95% CI 1.41-6.90) and MASLD (aHR 2.72, 95% CI 1.05-7.02). Conclusions: Fibrosis transitions are driven by metabolic health variables in PWH, independently of viral hepatitis coinfection and antiretroviral class therapy.

2023 - A call for health systems to monitor the health-related quality of life of people living with HIV [Articolo su rivista]
Lazarus, Jeffrey V; Van Hout, Marie Claire; Fuster-Ruizdeapodaca, Maria J; Brown, Graham; Guaraldi, Giovanni
abstract

Introduction: The World Health Organization's (WHO's) new global health strategy on HIV represents a major step toward a broader conceptualization of HIV care. It recognizes the importance of addressing chronic care more fully and-for the first time ever-the health-related quality of life (HRQoL) of people living with HIV (PLHIV).Methods: A thorough literature review was conducted in order to analyse how the WHO strategy on HIV for 2022-2030 addresses the monitoring of the HRQoL of PLHIV for the next decade and compared it to that of other countries and health authorities.Results: Unlike for other issues, the strategy does not include quantitative targets for 2030, thus falling short of committing to monitoring global progress in improving the long-term well-being of PLHIV.Conclusions: We urge national health systems not to wait for WHO to lead on this issue. Seeking good HRQoL outcomes for PLHIV can confer far-reaching benefits on health systems. The feasibility of monitoring population-level HRQoL has been demonstrated through the use of simple tools like patient-reported outcome measures (PROMs) and patient-reported experience measures (PREMs). Many countries can already set HRQoL monitoring targets, similar to those presented in this viewpoint, while we work toward an agreed minimum metric for use by all countries.

2023 - A Machine Learning Approach to Predict Weight Change in ART-Experienced People Living with HIV [Articolo su rivista]
Motta, F.; Milic, J.; Gozzi, L.; Belli, M.; Sighinolfi, L.; Cuomo, G.; Carli, F.; Dolci, G.; Iadisernia, V.; Burastero, G.; Mussini, C.; Missier, P.; Mandreoli, F.; Guaraldi, G.
abstract

Introduction:The objective of the study was to develop machine learning (ML) models that predict the percentage weight change in each interval of time in antiretroviral therapy-experienced people living with HIV.Methods:This was an observational study that comprised consecutive people living with HIV attending Modena HIV Metabolic Clinic with at least 2 visits. Data were partitioned in an 80/20 training/test set to generate 10 progressively parsimonious predictive ML models. Weight gain was defined as any weight change >5%, at the next visit. SHapley Additive exPlanations values were used to quantify the positive or negative impact of any single variable included in each model on the predicted weight changes.Results:A total of 3,321 patients generated 18,322 observations. At the last observation, the median age was 50 years and 69% patients were male. Model 1 (the only 1 including body composition assessed with dual-energy x-ray absorptiometry) had an accuracy greater than 90%. This model could predict weight at the next visit with an error of <5%.Conclusions:ML models with the inclusion of body composition and metabolic and endocrinological variables had an excellent performance. The parsimonious models available in standard clinical evaluation are insufficient to obtain reliable prediction, but are good enough to predict who will not experience weight gain.

2023 - BEING: Bone Health in Aging Women with HIV: Impact of Switching Antiretroviral Therapy on Bone Mineral Density During the Perimenopausal Period [Articolo su rivista]
Walmsley, Sharon; Clarke, Rosemarie; Lee, Terry; Singer, Joel; Cheung, Angela M; Smaill, Fiona; De Pokomandy, Alexandra; Trottier, Sylvia; Messina, Emanuela; Guaraldi, Giovanni
abstract

: Menopause is a high-risk period for osteoporosis, which may be exacerbated by HIV and/or antiretroviral therapy (ART). Our goal was to study the impact of switching from tenofovir disoproxil fumarate (TDF) to tenofovir alafenamide (TAF) on bone mineral density (BMD) in peri- and early postmenopausal women living with HIV. This is a randomized international multicenter study of an early versus delayed (48-week) switch. BMD was measured by dual energy X-ray absorptiometry scan. Thirty-four women were enrolled: 19 in the immediate and 15 in the delayed switch arm from September 2017 to April 2019; 30 completed the 96-week protocol. The study closed for futility during the COVID-19 pandemic. The median (intraquartile range [IQR]) age was 51 years (47, 53), with a median (IQR) of 16.5 years (14, 23) since HIV diagnosis, median (IQR) 14 years (11, 20) of ART, and mean 8.6 years TDF. At enrollment, TDF was used in combination with a boosted protease inhibitor (n = 7), a non-nucleoside reverse transcriptase inhibitor (n = 13), an integrase inhibitor (n = 11), or more than one ART class (n = 3). The median (95% confidence interval [CI]) percentage change in BMD at the lumbar spine from 0 to 48 weeks in the immediate switch group was 1.97% (-1.15 to 5.49) compared with a median (95% CI) decrease of 2.32% (-5.11 to 0.19) in the delayed arm. The median (95% CI) percentage change in BMD from 0 to 96 weeks was 2.33% (0-4.51) in the immediate arm compared with 0.70% (-3.19 to 2.47) in the delayed arm. We demonstrated a trend to increased BMD at the lumbar spine after a switch from TDF to TAF in peri- and early postmenopausal women living with HIV. Clinical Trials.gov: NCT02815566.

2023 - Bone Mineral Density and Trabecular Bone Score Changes throughout Menopause in Women with HIV [Articolo su rivista]
Milic, Jovana; Renzetti, Stefano; Morini, Denise; Motta, Federico; Carli, Federica; Menozzi, Marianna; Cuomo, Gianluca; Mancini, Giuseppe; Simion, Mattia; Romani, Federico; Spadoni, Anna; Baldisserotto, Irene; Barp, Nicole; Diazzi, Chiara; Mussi, Chiara; Mussini, Cristina; Rochira, Vincenzo; Calza, Stefano; Guaraldi, Giovanni
abstract

Objective: The objectives of this study were to describe the trajectories of bone mineral density (BMD) and trabecular bone score (TBS) changes throughout pre-menopause (reproductive phase and menopausal transition) and post-menopause (early and late menopause) in women with HIV (WWH) undergoing different antiretroviral therapies (ARTs) and explore the risk factors associated with those changes. Methods: This was an observational longitudinal retrospective study in WWH with a minimum of two DEXA evaluations comprising BMD and TBS measurements, both in the pre-menopausal and post-menopausal periods. Menopause was determined according to the STRAW+10 criteria, comprising four periods: the reproductive period, menopausal transition, and early- and late-menopausal periods. Mixed-effects models were fitted to estimate the trajectories of the two outcomes (BMD and TBS) over time. Annualized lumbar BMD and TBS absolute and percentage changes were calculated in each STRAW+10 time window. A backward elimination procedure was applied to obtain the final model, including the predictors that affected the trajectories of BMD or TBS over time. Results: A total of 202 WWH, all Caucasian, were included. In detail, 1954 BMD and 195 TBS data were analyzed. The median number of DEXA evaluations per woman was 10 (IQR: 7, 12). The median observation periods per patient were 12.0 years (IQR = 8.9-14.4) for BMD and 6.0 years (IQR: 4.3, 7.9) for TBS. The prevalence of osteopenia (63% vs. 76%; p < 0.001) and osteoporosis (16% vs. 36%; p < 0.001) increased significantly between the pre-menopausal and post-menopausal periods. Both BMD (1.03 (±0.14) vs. 0.92 (±0.12) g/cm2; p < 0.001) and TBS (1.41 (IQR: 1.35, 1.45) vs. 1.32 (IQR: 1.28, 1.39); p < 0.001) decreased significantly between the two periods. The trend in BMD decreased across the four STRAW+10 periods, with a slight attenuation only in the late-menopausal period when compared with the other intervals. The TBS slope did not significantly change throughout menopause. The delta mean values of TBS in WWH were lower between the menopausal transition and reproductive period compared with the difference between menopause and menopausal transition. Conclusions: Both BMD and TBS significantly decreased over time. The slope of the change in BMD and TBS significantly decreased in the menopausal transition, suggesting that this period should be considered by clinicians as a key time during which to assess bone health and modifiable risk factors in WWH.

2023 - Can statin preventative treatment inform geroscience-guided therapeutics? [Articolo su rivista]
Guaraldi, Giovanni; Erlandson, Kristine M; Milic, Jovana; Landay, Alan L; Montano, Monty A
abstract

: Potential senotherapeutic effect of statins may lead to prevention and reduction of frailty.

2023 - Comparing implications of cardiovascular risk of abacavir and integrase inhibitors: why scientific community is confused and timid? [Articolo su rivista]
Guaraldi, Giovanni; Milic, Jovana
abstract

2023 - Critical COVID-19 Patients Through First, Second And Third Wave: Retrospective Observational Study Comparing Outcomes In ICU. [Articolo su rivista]
Coloretti, Irene; Farinelli, Carlotta; Biagioni, Emanuela; Gatto, Ilenia; Munari, Elena; Dall’Ara, Lorenzo; Busani, Stefano; Meschiari, Marianna; Tonelli, Roberto; Mussini, Cristina; Guaraldi, Giovanni; Cossarizza, Andrea; Clini, Enrico; Girardis, Massimo
abstract

Introduction- The time-course of the COVID-19 pandemic was characterized by subsequent waves identified by peaks of Intensive Care Unit (ICU) admission rates. During these periods, progressive knowledge of the disease led to the development of specific therapeutic strategies. This retrospective study investigates whether this led to improvement in outcomes of COVID-19 patients admitted to ICU. Methods- Outcomes were evaluated in consecutive adult COVID19 patients admitted to our ICU, divided into three waves based on the admission period: the first wave from February 25th, 2020, to July 6th, 2020; the second wave from September 20th, 2020, to February 13th, 2021; the third wave from February 14th, 2021 to April 30th, 2021. Differences were assessed comparing outcomes and by using different multivariable Cox models adjusted for variables related to outcome. Further sensitivity analysis was performed in patients undergoing invasive mechanical ventilation. Results- Overall, 428 patients were included in the analysis: 102, 169 and 157 patients in the first, second and third wave. The ICU and in-hospital crude mortalities were lower by 7% and 10% in the third wave compared to the other 2 waves (p>0.05). A higher number of ICU and hospital free days at day 90 was found in the third wave when compared to the other 2 waves (p=0.001). Overall, 62.6% underwent invasive ventilation, with decreasing requirement during the waves (p=0.002). The adjusted Cox model showed no difference in the Hazard Ratio for mortality among the waves. In the propensity-matched analysis the hospital mortality rate was reduced by 11% in the third wave (p=0.044). Conclusions - With application of best practice as known by the time of the first three waves of the pandemic, our study failed to identify a significant improvement in mortality rate when comparing the different waves of the COVID-19 pandemic, notwithstanding, the sub-analyses showed a trend in mortality reduction in the third wave. Rather, our study identified a possible positive effect of dexamethasone on mortality rate reduction and the increased risk of death related to bacterial infections in the three waves.

2023 - Current Challenges and Solutions for Clinical Management and Care of People with HIV: Findings from the 12th Annual International HIV and Aging Workshop [Articolo su rivista]
Yu, Xiaoying; Lobo, Judith D; Sundermann, Erin; Baker, Darren J; Tracy, Russell P; Kuchel, George A; Stephenson, Kathryn E; Letendre, Scott L; Brew, Bruce; Cysique, Lucette A; Dale, Sannisha K; Wallen, Chelsie; Kunisaki, Ken M; Guaraldi, Giovanni; Milic, Jovana; Winston, Alan; Moore, David J; Margolick, Joseph B; Erlandson, Kristine M
abstract

People with HIV on combination antiretroviral therapy (ART) have longer life expectancy and are increasingly experiencing age-related comorbidities. Thus, aging with HIV has become a central issue in clinical care and research, which has been particularly challenging with the intersection of the ongoing coronavirus (COVID)-19 pandemic. Since 2009, the International Workshop on HIV and Aging has served as a multidisciplinary platform to share research findings from cross-disciplinary fields along with community advocates to address critical issues in HIV and aging. In this article, we summarize the key oral presentations from the 12th Annual International Workshop on HIV and Aging, held virtually on September 23rd and 24(th), 2021. The topics ranged from basic science research on biological mechanisms of aging to quality of life and delivery of care under the COVID-19 pandemic. This workshop enriched our understanding of HIV and aging under the COVID-19 pandemic, identified challenges and opportunities to combat the impact of COVID-19 on HIV communities, and also provided updated research and future directions of the field to move HIV and aging research forward, with the ultimate goal of successful aging for older people with HIV.

2023 - Detailed characterization of SARS-CoV-2-specific T and B cells after infection or heterologous vaccination [Articolo su rivista]
Lo Tartaro, Domenico; Paolini, Annamaria; Mattioli, Marco; Swatler, Julian; Neroni, Anita; Borella, Rebecca; Santacroce, Elena; Di Nella, Alessia; Gozzi, Licia; Busani, Stefano; Cuccorese, Michela; Trenti, Tommaso; Meschiari, Marianna; Guaraldi, Giovanni; Girardis, Massimo; Mussini, Cristina; Piwocka, Katarzyna; Gibellini, Lara; Cossarizza, Andrea; De Biasi, Sara
abstract

: The formation of a robust long-term antigen (Ag)-specific memory, both humoral and cell-mediated, is created following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or vaccination. Here, by using polychromatic flow cytometry and complex data analyses, we deeply investigated the magnitude, phenotype, and functionality of SARS-CoV-2-specific immune memory in two groups of healthy subjects after heterologous vaccination compared to a group of subjects who recovered from SARS-CoV-2 infection. We find that coronavirus disease 2019 (COVID-19) recovered patients show different long-term immunological profiles compared to those of donors who had been vaccinated with three doses. Vaccinated individuals display a skewed T helper (Th)1 Ag-specific T cell polarization and a higher percentage of Ag-specific and activated memory B cells expressing immunoglobulin (Ig)G compared to those of patients who recovered from severe COVID-19. Different polyfunctional properties characterize the two groups: recovered individuals show higher percentages of CD4+ T cells producing one or two cytokines simultaneously, while the vaccinated are distinguished by highly polyfunctional populations able to release four molecules, namely, CD107a, interferon (IFN)-γ, tumor necrosis factor (TNF), and interleukin (IL)-2. These data suggest that functional and phenotypic properties of SARS-CoV-2 adaptive immunity differ in recovered COVID-19 individuals and vaccinated ones.

2023 - Determinants of sexual function in men living with HIV younger than 50 years old: Focus on organic, relational, and psychological issues [Articolo su rivista]
De Vincentis, Sara; Decaroli, Maria Chiara; Milic, Jovana; Fanelli, Flaminia; Tartaro, Giulia; Diazzi, Chiara; Mezzullo, Marco; De Santis, Maria Cristina; Roli, Laura; Trenti, Tommaso; Santi, Daniele; Pagotto, Uberto; Guaraldi, Giovanni; Rochira, Vincenzo
abstract

Background: Sexual dysfunctions, particularly erectile dysfunction, are common in men living with HIV, whose organic and psychological components remain to be clarified. The aim of the study is to investigate the impact of risk factors of sexual dysfunctions, including organic, relational, and psychological determinants of erectile function, in men living with HIV younger than 50 years old. Methods: A cross-sectional, observational study was conducted in men living with HIV < 50 years. The questionnaire International Index of Erectile Function-15 was used to assess the prevalence and degree of erectile dysfunction. The structured interview of erectile dysfunction was used to explore the organic (Scale 1), relational (Scale 2), and psychological (Scale 3) components of erectile dysfunction. Total testosterone, estradiol, and dihydrotestosterone were measured by liquid chromatography-tandem-mass spectrometry; free testosterone was calculated by the Vermeulen equation. Results: A total of 313 consecutive men living with HIV were prospectively enrolled (median age 47.0 years; median HIV-infection duration 16.2 years). 187 patients (59.7%) had erectile dysfunction, with a higher prevalence of non-heterosexual (138 out of 187, 73.8%) than heterosexual patients (p = 0.003). Patients with erectile dysfunction showed a worse score of structured interview of erectile dysfunction scale 3 compared to patients without erectile dysfunction (p = 0.025); the International Index of Erectile Function-15 was inversely related to structured interview of erectile dysfunction scale 3 (p = 0.042). No difference was found for sex steroids (total testosterone, estradiol, free testosterone, and dihydrotestosterone) between men living with HIV with and without erectile dysfunction. In the multivariate analysis sexual orientation, and lack of stable relationships were major determinants for erectile dysfunction. Only 35 of 187 patients with erectile dysfunction (18.7%) reported the use of erectile dysfunction medications. Conclusions: Within the multidimensional network of erectile dysfunction in men living with HIV, the psychological component is predominant, highlighting the contribution of peculiar factors related to HIV distress (e.g., fear of virus transmission, stigma) rather than gonadal status and other classical risk factors. In contrast to the high prevalence, only a few patients reported the use of erectile dysfunction medications suggesting a general under-management of such issues.

2023 - Do all critically ill patients with COVID-19 disease benefit from adding tocilizumab to glucocorticoids? A retrospective cohort study. [Articolo su rivista]
Mussini, Cristina; Cozzi-Lepri, Alessandro; Meschiari, Marianna; Franceschini, Erica; Jole Burastero, Giulia; Faltoni, Matteo; Franceschi, Giacomo; Iadisernia, Vittorio; Volpi, Sara; Dessilani, Andrea; Gozzi, Licia; Conti, Jacopo; DEL MONTE, Martina; Milic, Jovana; Borghi, Vanni; Tonelli, Roberto; Brugioni, Lucio; Romagnoli, Elisa; Pietrangelo, Antonello; Corradini, Elena; Girardis, Massimo; Busani, Stefano; Cossarizza, Andrea; Clini, Enrico; Guaraldi, Giovanni
abstract

2023 - Drug treatment of COVID-19 infection [Articolo su rivista]
Lui, Grace; Guaraldi, Giovanni
abstract

Purpose of review: COVID-19 pandemic has caused more than 6.6 million deaths globally. Tremendous efforts have been committed for the development of new and repurposed drugs for the treatment of COVID-19. Although different international and national guidelines share consensus in the management of COVID-19 disease with different levels of severity, new challenges have emerged, steering the need for ongoing research in advancing the clinical management of COVID-19. Recent findings: This review focuses on recent data from randomized trials and postmarketing real-world evidence for the treatment of mild to moderate disease in the outpatient setting and patients hospitalized for COVID-19 with varying level of severity. Relevant data for treatment of the latest omicron sub-variants in people who received vaccination are presented. Challenges in special populations, including immunocompromised hosts, patients with renal failure and pregnant women, are also discussed. Summary: Treatment of COVID-19 should be personalized according to host characteristics, degree of severity and available treatment options.

2023 - Epidemiology and Prevention of Early Infections by Multi-Drug-Resistant Organisms in Adults Undergoing Liver Transplant: A Narrative Review [Articolo su rivista]
Dolci, Giovanni; Burastero, Giulia Jole; Paglia, Francesca; Cervo, Adriana; Meschiari, Marianna; Guaraldi, Giovanni; Chester, Johanna; Mussini, Cristina; Franceschini, Erica
abstract

Invasive bacterial infections are a leading cause of morbidity and mortality after liver transplant (LT), especially during the first months after LT, and infections due to multi-drug-resistant organisms (MDRO) are increasing in this setting. Most of the infections in patients in intensive care unit arise from the endogenous microflora and, for this reason, pre-LT MDRO rectal colonization is a risk factor for developing MDRO infections in the post-LT. Moreover, the transplanted liver may carry an increased risk of MDRO infections due to organ transportation and preservation, to donor intensive care unit stay and previous antibiotic exposure. To date, little evidence is available about how MDRO pre-LT colonization in donors and recipients should address LT preventive and antibiotic prophylactic strategies, in order to reduce MDRO infections in the post-LT period. The present review provided an extensive overview of the recent literature on these topics, with the aim to offer a comprehensive insight about the epidemiology of MDRO colonization and infections in adult LT recipients, donor-derived MDRO infections, possible surveillance, and prophylactic strategies to reduce post-LT MDRO infections.

2023 - Evaluating immunological and inflammatory changes of treatment-experienced people living with HIV switching from first-line triple cART regimens to DTG/3TC vs. B/F/TAF: the DEBATE trial [Articolo su rivista]
Cossarizza, A.; Cozzi-Lepri, A.; Mattioli, M.; Paolini, A.; Neroni, A.; De Biasi, S.; Tartaro, D. L.; Borella, R.; Fidanza, L.; Gibellini, L.; Beghetto, B.; Roncaglia, E.; Nardini, G.; Milic, J.; Menozzi, M.; Cuomo, G.; Digaetano, M.; Orlando, G.; Borghi, V.; Guaraldi, G.; Mussini, C.
abstract

Background: The aim of this randomized clinical trial (RCT) was to compare immunological changes in virally suppressed people living with HIV (PLWH) switching from a three-drug regimen (3DR) to a two-drug regimen (2DR).Methods: An open-label, prospective RCT enrolling PLWH receiving a 3DR who switched to bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) or dolutegravir/lamivudine (DTG/3TC) was performed. Blood was taken at baseline and months 6 and 12. The primary outcome was the change in CD4+ or CD8+ T-cell counts and CD4/CD8 ratio over time points. The secondary outcomes were the changes in immunological and inflammatory parameters. Parametric mixed-linear models with random intercepts and slopes were fitted separately for each marker after controlling for potential confounders.Results: Between the two arms (33 PLWH each), there was no difference in CD4+ or CD8+ T cells, CD4/CD8 ratio, and IL-6 trajectories. PLWH switching to DTG/3TC had increased levels of both transitional memory and terminally differentiated CD4+ T cells (arm-time interaction p-value = 0.02) and to a lesser extent for the corresponding CD8+ T-cell subsets (p = 0.09). Significantly lower levels of non-classical monocytes were detected in the B/F/TAF arm at T6 (diff = -6.7 cells/mm(3); 95% CI; -16, +2.6; p-value for interaction between arm and time = 0.03). All differences were attenuated at T12.Conclusion: No evidence for a difference in absolute CD4+ and CD8+ T-cell counts, CD4/CD8 ratio, and IL-6 trajectories by study arm over 12 months was found. PLWH on DTG/3TC showed higher levels of terminally differentiated and exhausted CD4+ and CD8+ T lymphocytes and non-classical monocytes at T6. Further studies are warranted to better understand the clinical impact of our results.

2023 - Evidence gaps on weight gain in people living with HIV: a scoping review to define a research agenda [Articolo su rivista]
Guaraldi, Giovanni; Bonfanti, Paolo; Di Biagio, Antonio; Gori, Andrea; Milić, Jovana; Saltini, Paola; Segala, Francesco V; Squillace, Nicola; Taramasso, Lucia; Cingolani, Antonella
abstract

Background: Combined antiretroviral therapy (cART) dramatically improved survival in people living with HIV (PLWH) but is associated with weight gain (WG), raising concern for a possible obesity epidemic in PLWH. This scoping review aims to identify the gaps in the existing evidence on WG in PLWH and generate a future research agenda. Methods: This review was conducted according to the methodology for scoping studies and reported according to the PRISMA Extension for Scoping Review checklist. Articles published in English in the last 10 years indexed in Pubmed, WHO Global Index Medicus, or Embase were searched using specific queries focused on WG in PLWH. Results: Following the selection process, 175 included articles were reviewed to search for the available evidence on four specific topics: (I) definition of WG in PLWH, (II) pathogenesis of WG in PLWH, (III) impact of ART on WG, (IV) correlation of WG with clinical outcomes. A summary of the data enabled us to identify gaps and clearly define the following research agenda: (I) develop a data-driven definition of WG in PLWH and define noninvasive assessment methods for body weight and fat composition; (II) further investigate the interaction between HIV/cART and immunity, metabolism, and adipose tissue; (III) establish the specific role of individual drugs on WG; (IV) clarify the independent role of WG, cART, HIV, and metabolic factors on clinical events. Conclusions: The proposed research agenda may help define future research and fill the knowledge gaps that have emerged from this review.

2023 - Fibroscan-aspartate aminotransferase (FAST) score predicts liver-related outcomes, but not extra-hepatic events, in a multicenter cohort of people with HIV [Articolo su rivista]
Sebastiani, Giada; Milic, Jovana; Kablawi, Dana; Gioe', Claudia; Al Hinai, Al Shaima; Lebouché, Bertrand; Tsochatzis, Emmanuel; Finkel, Jemima; Ballesteros, Luz Ramos; Ramanakumar, Agnihotram V; Bhagani, Sanjay; Benmassaoud, Amine; Mazzola, Giovanni; Cascio, Antonio; Guaraldi, Giovanni
abstract

Background: Nonalcoholic fatty liver disease (NAFLD) is frequent in people with HIV (PWH). The Fibroscan-aspartate aminotransferase (FAST) score was developed to identify patients with nonalcoholic steatohepatitis (NASH) and significant fibrosis. We investigated prevalence of NASH with fibrosis and the value of FAST score in predicting clinical outcomes in PWH. Methods: Transient elastography (Fibroscan) was performed in PWH without viral hepatitis coinfection from four prospective cohorts. We used FAST>0.35 to diagnose NASH with fibrosis. Incidence and predictors of liver-related outcomes (hepatic decompensation, hepatocellular carcinoma) and extra-hepatic events (cancer, cardiovascular disease) were evaluated through survival analysis. Results: Of the 1472 PWH included, 8% had FAST>0.35. On multivariable logistic regression, higher BMI (adjusted odds ratio [aOR] 1.21, 95% confidence interval [CI] 1.14-1.29), hypertension (aOR 2.24, 95% CI 1.16-4.34), longer time since HIV diagnosis (aOR 1.82, 95% CI 1.20-2.76) and detectable HIV viral load (aOR 2.22, 95% CI 1.02-4.85) were associated with FAST>0.35. 882 patients were followed for a median of 3.8 years (interquartile range 2.5-4.2). Overall, 2.9% and 11.1% developed liver-related and extra-hepatic outcomes, respectively. Incidence of liver-related outcomes was higher in patients with FAST>0.35 vs. FAST<0.35 (45.1, 95% CI 26.2-77.7 vs. 5.0, 95% 2.9-8.6 per 1000 person-years). On multivariable Cox regression analysis, FAST>0.35 remained an independent predictor of liver-related outcomes (adjusted hazard ratio 4.97, 95% CI 1.97-12.51). Conversely, FAST did not predict extra-hepatic events. Conclusion: A significant proportion of PWH without viral hepatitis coinfection may have NASH with significant liver fibrosis. FAST score predicts liver-related outcomes and can help risk stratification and management in this high-risk population.

2023 - Impact of coronavirus disease 2019 on co-morbidities in HIV [Articolo su rivista]
Guaraldi, Giovanni; Milic, Jovana
abstract

2023 - Incidence of hypertension and blood pressure changes in persons with HIV at high risk for cardiovascular disease switching from boosted protease inhibitors to dolutegravir: a post-hoc analysis of the 96-week randomised NEAT-022 trial [Articolo su rivista]
Sempere, Abiu; Assoumou, Lambert; González-Cordón, Ana; Waters, Laura; Rusconi, Stefano; Domingo, Pere; Gompels, Mark; de Wit, Stephane; Raffi, François; Stephan, Christoph; Masiá, Mar; Rockstroh, Jürgen; Katlama, Christine; Behrens, Georg M N; Moyle, Graeme; Johnson, Margaret; Fox, Julie; Stellbrink, Hans-Jürgen; Guaraldi, Giovanni; Florence, Eric; Esser, Stefan; Gatell, José; Pozniak, Anton; Martínez, Esteban
abstract

Background: Integrase inhibitors have been recently linked to a higher risk for hypertension. In NEAT022 randomized trial, virologically suppressed persons with HIV (PWH) with high cardiovascular risk switched from protease inhibitors to dolutegravir either immediately (DTG-I) or after 48 weeks (DTG-D). Methods: Primary endpoint was incident hypertension at 48 weeks. Secondary endpoints were changes in systolic (SBP) and diastolic (DBP) blood pressure; adverse events and discontinuations associated with high blood pressure; and factors associated with incident hypertension. Results: At baseline, 191 (46.4%) participants had hypertension and 24 persons without hypertension were receiving antihypertensive medications for other reasons. In the 197 PWH (n=98, DTG-I arm; n=99, DTG-D arm) without hypertension or antihypertensive agents at baseline, incidence rates per 100 person-years were 40.3 and 36.3 (DTG-I) and 34.7 and 52.0 (DTG-D) at 48 (P=0. 5755) and 96 (P=0. 2347) weeks. SBP or DBP changes did not differed between arms. DBP (mean, 95% confidence interval) significantly increased in both DTG-I (+2.78 mmHg (1.07-4.50), P=0.0016] and DTG-D [+2.29 mmHg (0.35-4.23), P=0.0211] arms in the first 48 weeks of exposure to dolutegravir. Four (3 under dolutegravir, 1 under protease inhibitors) participants discontinued study drugs due to adverse events associated with high blood pressure. Classical factors, but not treatment arm, were independently associated with incident hypertension. Conclusions: PWH at high risk for cardiovascular disease showed high rates of hypertension at baseline and after 96 weeks. Switching to dolutegravir did not negatively impact on the incidence of hypertension or blood pressure changes relative to continuing protease inhibitors.

2023 - Letter to the editor: People living with HIV and NAFLD: A population left behind in the global effort for liver fibrosis screening? [Articolo su rivista]
Sebastiani, Giada; Milic, Jovana; Tsochatzis, Emmanuel A; Marzolini, Catia; Betel, Michael; Bhagani, Sanjay; Morse, Caryn G; Cinque, Felice; Maurice, James B; Ingiliz, Patrick; Price, Jennifer; Lemoine, Maud; Rockstroh, Jürgen K; Guaraldi, Giovanni
abstract

2023 - Limited weight impact after switching from boosted protease inhibitors to dolutegravir in persons with HIV with high cardiovascular risk: a post hoc analysis of the 96-week NEAT-022 randomized trial [Articolo su rivista]
Waters, Laura; Assoumou, Lambert; González-Cordón, Ana; Rusconi, Stefano; Domingo, Pere; Gompels, Mark; de Wit, Stephane; Raffi, François; Stephan, Christoph; Masiá, Mar; Rockstroh, Jürgen; Katlama, Christine; Behrens, Georg M N; Moyle, Graeme; Johnson, Margaret; Fox, Julie; Stellbrink, Hans-Jürgen; Guaraldi, Giovanni; Florence, Eric; Esser, Stefan; Gatell, José M; Pozniak, Anton; Martínez, Esteban
abstract

Background In the NEAT022 trial, virologically suppressed persons with human immunodeficiency virus (HIV) at high cardiovascular risk switching from protease inhibitors to dolutegravir either immediately (DTG-I) or after 48 weeks (DTG-D) showed noninferior virological suppression and significant lipid and cardiovascular disease risk reductions on switching to dolutegravir relative to continuing protease inhibitors. Methods In post hoc analysis, major endpoints were 48-week and 96-week weight and body mass index (BMI) changes. Factors associated with weight/BMI changes within the first 48 weeks of DTG exposure, proportion of participants by category of percentage weight change, proportions of BMI categories over time, and impact on metabolic outcomes were also assessed. Results Between May 2014 and November 2015, 204 (DTG-I) and 208 (DTG-D) participants were included. Weight significantly increased (mean, +0.810 kg DTG-I arm, and +0.979 kg DTG-D arm) in the first 48 weeks postswitch, but remained stable from 48 to 96 weeks in DTG-I arm. Switching from darunavir, White race, total to high-density lipoprotein cholesterol ratio <3.7, and normal/underweight BMI were independently associated with higher weight/BMI gains. The proportion of participants with >= 5% weight change increased similarly in both arms over time. The proportions of BMI categories, use of lipid-lowering drugs, diabetes and/or use of antidiabetic agents, and hypertension and/or use of antihypertensive agents did not change within or between arms at 48 and 96 weeks. Conclusions Switching from protease inhibitors to dolutegravir in persons with HIV with high cardiovascular risk led to modest weight gain limited to the first 48 weeks, which involved preferentially normal-weight or underweight persons and was not associated with negative metabolic outcomes.Switching from protease inhibitors to dolutegravir in persons with HIV with high cardiovascular risk led to modest weight gain limited to the first 48 weeks, which involved preferentially normal-weight or underweight persons and was not associated with negative metabolic outcomes.

2023 - Long-Covid-19 Dysphagia: proposal of a standardized evaluation protocol and disease description [Articolo su rivista]
Caragli, V; Guarnaccia, Mc; Pingani, L; Boca, S; Dondi, F; Genovese, E; Guaraldi, G; Farneti, D.
abstract

2023 - Long-term effects on subclinical cardiovascular disease of switching from boosted protease inhibitors to dolutegravir [Articolo su rivista]
González-Cordón, Ana; Assoumou, Lambert; Moyle, Graeme; Waters, Laura; Johnson, Margaret; Domingo, Pere; Fox, Julie; Stellbrink, Hans-Jürgen; Guaraldi, Giovanni; Masiá, Mar; Gompels, Mark; De Wit, Stephane; Florence, Eric; Esser, Stefan; Raffi, François; Behrens, Georg; Pozniak, Anton; Gatell, Jose M; Martínez, Esteban
abstract

Background In the NEAT022 trial, switching from boosted PIs (PI/r) to dolutegravir in people with HIV (PWH) with high cardiovascular risk decreased plasma lipids, soluble CD14 and adiponectin, and showed consistent favourable, although non-significant, effects on carotid intima-media thickness (CIMT) progression at 48 weeks. We hereby communicate planned final 96 week results on biomarker changes and CIMT progression. Methods PWH on a PI/r-based triple therapy regimen were randomly assigned (1:1) to switch the PI/r component to dolutegravir either immediately (DTG-I group) or after 48 weeks (DTG-D group) and were followed up to 96 weeks. We assessed changes in biomarkers associated with inflammation, endothelial dysfunction, monocyte immune activation, oxidation, insulin resistance, hypercoagulability, heart failure, myocardial injury and glomerular and tubular kidney injury, and right and left CIMT progression at 48 and 96 weeks. Results Of 415 PWH randomized, 287 (69%) and 143 (34%) contributed to the biomarker and CIMT substudies respectively. There were significant 96 week changes in biomarkers associated with inflammation, immune activation, oxidation, insulin resistance and myocardial injury. Most changes were favourable, except for adiponectin reduction, which may suggest higher insulin resistance. We were unable to detect significant changes in the progression of CIMT between arms or within arms at 96 weeks. Discussion After 96 weeks, switching from PI/r to dolutegravir in PWH with high cardiovascular risk led to significant changes in several biomarkers associated with cardiovascular disease. Although most changes were favourable, adiponectin reduction was not. There were non-significant changes in CIMT progression.

2023 - Long-term success for people living with HIV: A framework to guide practice [Articolo su rivista]
Lazarus, Jeffrey V; Wohl, David A; Cascio, Mario; Guaraldi, Giovanni; Rockstroh, Jürgen; Hodson, Matthew; Richman, Bruce; Brown, Gina; Anderson, Jane; Fuster-RuizdeApodaca, Maria J
abstract

Objectives: In recent decades, the needs of people living with HIV have evolved as life expectancy has greatly improved. Now, a new definition of long-term success (LTS) is necessary to help address the multifaceted needs of all people living with HIV. Methods: We conducted a two-phase research programme to delineate the range of experiences of people living with HIV. The insights garnered from these research phases were explored in a series of expert-led workshops, which led to the development and refinement of the LTS framework. Results: The insights generated from the research phases identified a series of themes that form a part of LTS. These themes were subsequently incorporated into the LTS framework, which includes five outcome pillars: sustained undetectable viral load, minimal impact of treatment and clinical monitoring, optimized health-related quality of life, lifelong integration of healthcare, and freedom from stigma and discrimination. A series of supporting statements were also developed by the expert panel to help in the achievement of each of the LTS pillars. Conclusions: The LTS framework offers a comprehensive and person-centric approach that, if achieved, could help improve the long-term well-being of people living with HIV and support the LTS vision of 'every person living with HIV being able to live their best life'.

2023 - Major revision version 12.0 of the European AIDS Clinical Society guidelines 2023 [Articolo su rivista]
Ambrosioni, Juan; Levi, Laura; Alagaratnam, Jasmini; Van Bremen, Kathrin; Mastrangelo, Andrea; Waalewijn, Hylke; Molina, Jean-Michel; Guaraldi, Giovanni; Winston, Alan; Boesecke, Christoph; Cinque, Paola; Bamford, Alasdair; Calmy, Alexandra; Marzolini, Catia; Martínez, Esteban; Oprea, Cristiana; Welch, Steven; Koval, Anna; Mendao, Luis; Rockstroh, Jürgen K
abstract

Background The European AIDS Clinical Society (EACS) guidelines were revised in 2023 for the 19th time, and all aspects of HIV care were updated.Key Points of the Guidelines Update Version 12.0 of the guidelines recommend the same six first-line treatment options for antiretroviral treatment (ART)-naive adults as versions 11.0 and 11.1: tenofovir-based backbone plus an unboosted integrase inhibitor or doravirine; abacavir/lamivudine plus dolutegravir; or dual therapy with lamivudine or emtricitabine plus dolutegravir. The long-acting section has been expanded in the ART and drug-drug interaction (DDI) panels. Tables for preferred and alternative ART in children and adolescents have been updated, as has the section on prevention of vertical transmission, particularly with new guidance for breastfeeding. A new DDI table has been included for the ART and anti-infective drugs used for opportunistic infections, sexually transmitted infections, and other infectious conditions; lenacapavir has been included in all DDI tables. New sections on alcohol use and patient-reported outcome measures (PROMs) have been included in the comorbidity panel, in addition to updates on many relevant topics, such as new resource guidance for deprescribing in people with HIV. Other sections, including travel, cognitive impairment, cancer screening, sexual health, and diabetes have also been revised extensively. The algorithm for the management of acute hepatitis C virus infection has been removed, as current guidelines recommend immediate treatment of all people with recently acquired hepatitis C virus. Updates on vaccination for hepatitis B virus and recommendations for simplification to tenofovir-free two-drug regimens in people with isolated anti-hepatitis B core antibodies are provided. In the opportunistic infections and COVID-19 panel, guidance on the management of COVID-19 in people with HIV has been updated according to the most up-to-date evidence, and a new section on monkeypox has been added.Conclusions In 2023, the EACS guidelines were updated extensively and now include several new sections. The recommendations are available as a free app, in interactive web format, and as a pdf online.

2023 - Masticatory Functionality in Post-Acute-COVID-Syndrome (PACS) Patients with and without Sarcopenia [Articolo su rivista]
Pugliese, BRUNO DAVIDE; Garuti, Giovanna; Bergamini, Lucia; Khamaisi, RICCARDO KARIM; Guaraldi, Giovanni; Consolo, Ugo; Bellini, Pierantonio
abstract

Musculoskeletal symptoms are common in both acute COVID-19 disease and post-acute sequelae (Post-Acute COVID Syndrome). The purpose of this study is to investigate whether there are reduced levels of masticatory function in patients with PACS (Post Acute COVID Syndrome) who suffer from sarcopenia, under the hypothesis that the latter may also involve the masticatory muscles. This study includes 23 patients hospitalized for COVID-19 between February 2020 and April 2021 and currently suffering from PACS. Among these PACS patients, 13/23 (56%) suffer from sarcopenia, 5/23 (22%) complain of asthenia but do not suffer from sarcopenia and the remaining 5/23 (22%) do not present muscle symptoms (non-asthenic non-sarcopenic). Oral health indices of all patients were collected. The masticatory strength was assessed with a gnathodynamometer based on piezoresistive sensors, and the masticatory effectiveness was measured by administering the “chewing gum mixing ability test” by having patients perform 20 masticatory cycles on a two-color chewing gum and analyzing the outcome through the ViewGum© software. Moreover, we gathered data with a hand grip test and gait speed test. The data collected in this study show that PACS sarcopenic patients have decreased masticatory effectiveness and strength compared to PACS asthenic non-sarcopenic patients and PACS non-asthenic non-sarcopenic patients.

2023 - Moving from the prediction of fractures to the prediction of falls in an aging HIV scenario [Articolo su rivista]
Milic, Jovana; Erlandson, Kristine M; Guaraldi, Giovanni
abstract

2023 - Nutritional and Lifestyle Therapy for NAFLD in People with HIV [Articolo su rivista]
Cinque, Felice; Cespiati, Annalisa; Lombardi, Rosa; Guaraldi, Giovanni; Sebastiani, Giada
abstract

HIV infection and nonalcoholic fatty liver disease (NAFLD) are two major epidemics affecting millions of people worldwide. As people with HIV (PWH) age, there is an increased prevalence of metabolic comorbidities, along with unique HIV factors, such as HIV chronic inflammation and life-long exposure to antiretroviral therapy, which leads to a high prevalence of NAFLD. An unhealthy lifestyle, with a high dietary intake of refined carbohydrates, saturated fatty acids, fructose added beverages, and processed red meat, as well as physical inactivity, are known to trigger and promote the progression of NAFLD to nonalcoholic steatohepatitis, liver fibrosis, and hepatocellular carcinoma. Furthermore, with no currently approved pharmacotherapy and a lack of clinical trials that are inclusive of HIV, nutritional and lifestyle approaches still represent the most recommended treatments for PWH with NAFLD. While sharing common features with the general population, NAFLD in PWH displays its own peculiarities that may also reflect different impacts of nutrition and exercise on its onset and treatment. Therefore, in this narrative review, we aimed to explore the role of nutrients in the development of NAFLD in PWH. In addition, we discussed the nutritional and lifestyle approaches to managing NAFLD in the setting of HIV, with insights into the role of gut microbiota and lean NAFLD.

2023 - Persistent SARS-CoV-2 infection with multiple clinical relapses in two patients with follicular lymphoma treated with bendamustine and obinutuzumab or rituximab [Articolo su rivista]
Franceschini, Erica; Pellegrino, Mariachiara; Todisco, Vera; Dolci, Giovanni; Bettelli, Francesca; Meschiari, Marianna; Bedini, Andrea; Fregni-Serpini, Giulia; Grottola, Antonella; Guaraldi, Giovanni; Pecorari, Monica; Sarti, Mario; Luppi, Mario; Perno, Carlo Federico; Mussini, Cristina
abstract

Purpose: People with hematologic malignancies have a significantly higher risk of developing severe and protracted forms of SARS-CoV-2 infection compared to immunocompetent patients, regardless of vaccination status. Results: We describe two cases of prolonged SARS-CoV-2 infection with multiple relapses of COVID-19 pneumonia in patients with follicular lymphoma treated with bendamustine and obinutuzumab or rituximab. The aim is to highlight the complexity of SARS-CoV-2 infection in this fragile group of patients and the necessity of evidence-based strategies to treat them properly. Conclusions: Patients with hematological malignancies treated with bendamustine and anti-CD20 antibodies had a significant risk of prolonged and relapsing course of COVID-19. Specific preventive and therapeutic strategies should be developed for this group of patients.

2023 - Practical management of complexity in older people with HIV: approaching an international consensus [Articolo su rivista]
Barber, Tristan J; Crabtree, Brenda; Cortes, Claudia P; Guaraldi, Giovanni; Hoy, Jennifer F; Rajasuriar, Renna; Castilho, Jessica; Agosto-Rosario, Moisés; Murzin, Kate; Falutz, Julian
abstract

: ABSTRACTGlobally the community of people with HIV is ageing, and some of these have increasingly complex care needs, with a known excess of non-HIV related comorbidities and related issues including consequent polypharmacy. At the 2022 International AIDS Conference in Montréal, Canada, the "Silver Zone" was created in the Global Village as a safe space for older people with HIV. As part of the Silver Zone activities, a session discussing global models of care for in this group was held. HIV treatment providers and advocates from diverse resource settings and with a diversity of expertise were invited to share their experience, reflections, and ideas, and this consensus statement was formed based on these discussions. Different approaches to care emerged, based on local needs and resources, and it became clear that issues of complexity and frailty need not be age limited. Despite clear regional differences, some common themes became apparent, and a consensus was established on basic principles that may be considered in diverse settings. These are discussed here, with agreement on necessary proximal steps to develop bespoke person-centred care models.

2023 - Prevalence, clinical course and outcomes of COVID-19 in peritoneal dialysis (PD) patients: a single-center experience [Articolo su rivista]
Alfano, Gaetano; Fontana, Francesco; Giovanella, Silvia; Morisi, Niccolo; Amurri, Alessio; Ligabue, Giulia; Guaraldi, Giovanni; Ferrari, Annachiara; Cappelli, Gianni; Magistroni, Riccardo; Gregorini, Mariacristina; Donati, Gabriele
abstract

Introduction There are limited data on the effects of COVID-19 on peritoneal dialysis (PD) patients. This study aimed to describe the impact of COVID-19 on the PD population. Methods A monocentric retrospective observational study was conducted on 146 consecutive PD patients followed from January 2020 to March 2022 at the University Hospital of Modena, Italy. Results Twenty-seven (18.4%) PD patients experienced 29 episodes of SARS-CoV-2 infection, corresponding to an incidence rate of 0.16 episodes/patient-year. Median age of COVID-19 patients was 60.4 (interquartile range [IQR] 50.2-66.5) years. In unvaccinated patients (n. 9), COVID-19 was always symptomatic and manifested with fever (100%) and cough (77.7%). COVID-19 caused hospital admission of three (33.3%) patients and two (22.2%) died of septic shock. COVID-19 was symptomatic in 83.3% of vaccinated subjects (n.18) and manifested with fever (61.1%) and cough (55.6%). Hospital admission occurred in 27.8% of the subjects but all were discharged home. Median SARS-CoV-2 shedding was 32 and 26 days in the unvaccinated and vaccinated groups, respectively. At the end of the follow-up, COVID-19 triggered the shift from PD to HD in two subjects without affecting the residual renal function of the remaining patients. Overall, COVID-19 caused an excess death of 22.2%. COVID-19 vaccination refusal accounted for only 1.6% in this cohort of patients. Conclusion COVID-19 incident rate was 0.16 episodes/patient-year in the PD population. About one-third of the patients were hospitalized for severe infection. Fatal outcome occurred in two (7.4%) unvaccinated patients. A low vaccination refusal rate was observed in this population.

2023 - Prognostic immune markers identifying patients with severe COVID-19 who respond to tocilizumab [Articolo su rivista]
DE BIASI, Sara; Mattioli, Marco; Meschiari, Marianna; LO TARTARO, Domenico; Paolini, Annamaria; Borella, Rebecca; Neroni, Anita; Fidanza, Lucia; Busani, Stefano; Girardis, Massimo; Coppi, Francesca; Mattioli, Anna Vittoria; Guaraldi, Giovanni; Mussini, Cristina; Cossarizza, Andrea; Gibellini, Lara
abstract

Introduction: A growing number of evidences suggest that the combination of hyperinflammation, dysregulated T and B cell response and cytokine storm play a major role in the immunopathogenesis of severe COVID-19. IL-6 is one of the main pro-inflammatory cytokines and its levels are increased during SARS-CoV-2 infection. Several observational and randomized studies demonstrated that tocilizumab, an IL-6R blocker, improves survival in critically ill patients both in infectious disease and intensive care units. However, despite transforming the treatment options for COVID-19, IL-6R inhibition is still ineffective in a fraction of patients. Methods: In the present study, we investigated the impact of two doses of tocilizumab in patients with severe COVID-19 who responded or not to the treatment by analyzing a panel of cytokines, chemokines and other soluble factors, along with the composition of peripheral immune cells, paying a particular attention to T and B lymphocytes. Results: We observed that, in comparison with non-responders, those who responded to tocilizumab had different levels of several cytokines and different T and B cells proportions before starting therapy. Moreover, in these patients, tocilizumab was further able to modify the landscape of the aforementioned soluble molecules and cellular markers. Conclusions: We found that tocilizumab has pleiotropic effects and that clinical response to this drug remain heterogenous. Our data suggest that it is possible to identify patients who will respond to treatment and that the administration of tocilizumab is able to restore the immune balance through the re-establishment of different cell populations affected by SARS-COV-2 infection, highlighting the importance of temporal examination of the pathological features from the diagnosis.

2023 - Prognostic value of non-invasive scores based on liver stiffness measurement, spleen diameter and platelets in HIV-infected patients [Articolo su rivista]
Benmassaoud, Amine; Macias, Juan; Delamarre, Adèle; Corma-Gomez, Anaïs; Guaraldi, Giovanni; Milic, Jovana; Rockstroh, Jürgen K; Van Bremen, Kathrin; Tsochatzis, Emmanuel; Mulay, Akhilesh; Price, Jennifer; Garvey, Lucy J; Lemoine, Maud; Kablawi, Dana; Lebouche, Bertrand; Klein, Marina B; Ballesteros, Luz R; Boesecke, Christopher; Schepis, Filippo; Bhagani, Sanjay; Cooke, Graham; Berzigotti, Annalisa; Hirose, Kyoko; Pineda, Juan A; Ramanakumar, Agnihotram V; De-Ledinghen, Victor; Saeed, Sahar; Sebastiani, Giada
abstract

Background and aims: People living with HIV (PLWH) are at high risk for advanced chronic liver disease and related adverse outcomes. We aimed to validate the prognostic value of non-invasive scores based on liver stiffness measurement (LSM) and on markers of portal hypertension (PH), namely platelets and spleen diameter, in PLWH. Methods: We combined data from eight international cohorts of PLWH with available non-invasive scores, including LSM and the composite biomarkers liver stiffness-spleen size-to-platelet ratio score (LSPS), LSM-to-Platelet ratio (LPR) and PH risk score. Incidence and predictors of all-cause mortality, any liver-related event and classical hepatic decompensation were determined by survival analysis, controlling for competing risks for the latter two. Non-invasive scores were assessed and compared using area under the receiver operating curve (AUROC). Results: We included 1695 PLWH (66.8% coinfected with hepatitis C virus). During a median follow-up of 4.7 (interquartile range 2.8-7.7) years, the incidence rates of any liver-related event, all-cause mortality and hepatic decompensation were 13.7 per 1000 persons-year (PY) (95% confidence interval [CI], 11.4-16.3), 13.8 per 1000 PY (95% CI, 11.6-16.4) and 9.9 per 1000 PY (95% CI, 8.1-12.2), respectively. The AUROC of LSM was similar to that of the composite biomarkers, ranging between 0.83 and 0.86 for any liver-related event, 0.79-0.85 for all-cause mortality and 0.87-0.88 for classical hepatic decompensation. All individual non-invasive scores remained independent predictors of clinical outcomes in multivariable analysis. Conclusions: Non-invasive scores based on LSM, spleen diameter and platelets predict clinical outcomes in PLWH. Composite biomarkers do not achieve higher prognostic performance compared to LSM alone.

2023 - Prolonged RT-PCR test positivity in hemodialysis patients with COVID-19 [Articolo su rivista]
Alfano, G.; Morisi, N.; Ferri, C.; Fontana, F.; Giovanella, S.; Ligabue, G.; Mori, G.; Franceschini, E.; Ferrari, A.; Gregorini, M.; Cappelli, G.; Tagliazucchi, S.; Pecorari, M.; Guaraldi, G.; Magistroni, R.; Donati, G.
abstract

Background: The weakened immune system of patients on hemodialysis (HD) may prolong SARS-CoV-2 infection compared to the general population. Current international guidelines recommend ending isolation in conjunction with serial testing in moderately and severely immunocompromised subjects. This study aimed to estimate SARS-CoV-2 infectivity by measuring RT-PCR test positivity in HD patients. A comparison between RT-PCR test and cycle threshold (Ct) value has been performed as a secondary endpoint. Methods: A single-center retrospective study was conducted at the University of Modena (Italy) from March 2020 to October 2022. Only patients on chronic HD therapy with COVID-19 were enrolled in the study. In our HD Center, two negative nasopharyngeal reverse transcription polymerase chain reaction (RT-PCR) results were used to end quarantine in this population. SARS-CoV-2 RT-PCR test positivity duration measured the time elapsed from a positive RT-PCR to a second negative test. Ct cut-off of 35 cycles was used to definite “high Ct value,” a condition characterized by a large number of cycles of PCR amplification to register a positive RT-PCR test. Results: During the observational period, 159 cases of SARS-CoV-2 infections were diagnosed in 151 patients. Median age was 70.1 (54.3–81.6) years and males accounted for 59.6% of the COVID-19 population. Median duration of SARS-CoV-2 RT-PCR test positivity on the nasal mucosa accounted for 30 (IQR, 21–40.5) days. Unvaccinated patients experienced significantly longer RT-PCR test positivity compared to vaccinated patients (42 [IQR,31–56] vs. 28 [IQR,20–35.7] days; p = < 0.001). The use of high Ct value, a laboratory surrogate of SARS-CoV-2 replication, anticipated a negative RT-PCR test of 9 (IQR, 6–12) days. Multivariate linear regression analysis showed that increased age (β coefficient 0.31; confidence interval [CI] 95%, 0.14—0.43; p = < 0.001) and the lack of anti-SARS-CoV-2 vaccination (β 0.49 CI95%, 11.9–22.5; p = < 0.001) were predictors of a prolonged RT-PCR positivity. Conclusions: Patients with COVID-19 on HD had prolonged RT-PCR test positivity. The adoption of “high Ct value” criteria led to a significant reduction in the duration of RT-PCR test positivity compared to the use of the classical nucleic acid amplification test. In our study, the lack of SARS-CoV-2 vaccination and older age were independently associated with a longer RT-PCR positivity.

2023 - Quality of life and intrinsic capacity in patients with post-acute COVID-19 syndrome is in relation to frailty and resilience phenotypes. [Articolo su rivista]
Guaraldi, Giovanni; Milic, Jovana; Barbieri, Sara; Marchio', Tommaso; Caselgrandi, Agnese; Motta, Federico; Beghe', Bianca; Verduri, Alessia; Belli, Michela; Gozzi, Licia; Iadisernia, Vittorio; Faltoni, Matteo; Burastero, Giulia; Dessilani, Andrea; DEL MONTE, Martina; Dolci, Giovanni; Bacca, Erica; Franceschi, Giacomo; Yaacoub, Dina; Volpi, Sara; Mazzochi, Alice; Clini, Enrico; Mussini, Cristina
abstract

Background- The objective of this study was to characterize frailty and resilience in people evaluated for Post-Acute COVID-19 Syndrome (PACS), in relation to quality of life (QoL) and Intrinsic Capacity (IC). Methods- This cross-sectional, observational, study included consecutive people previously hospitalized for severe COVID-19 pneumonia attending Modena (Italy) PACS Clinic from July 2020 to April 2021. Four frailty-resilience phenotypes were built: “fit/resilient”, “fit/non-resilient”, “frail/resilient” and “frail/non-resilient”. Frailty and resilience were defined according to frailty phenotype and Connor Davidson resilience scale (CD-RISC-25) respectively. Study outcomes were: QoL assessed by means of Symptoms Short form health survey (SF-36) and health-related quality of life (EQ-5D-5L) and IC by means of a dedicated questionnaire. Their predictors including frailty-resilience phenotypes were explored in logistic regressions. Results- 232 patients were evaluated, median age was 58.0 years. PACS was diagnosed in 173 (74.6%) patients. Scarce resilience was documented in 114 (49.1%) and frailty in 72 (31.0%) individuals. Predictors for SF-36 score <61.60 were the phenotypes “frail/non-resilient” (OR=4.69, CI:2.08-10.55), “fit/non-resilient” (OR=2.79, CI:1.00-7.73). Predictors for EQ-5D-5L <89.7% were the phenotypes “frail/non-resilient” (OR=5.93, CI: 2.64-13.33) and “frail/resilient” (OR=5.66, CI:1.93-16.54). Predictors of impaired IC (below the mean score value) were “frail/non-resilient” (OR=7.39, CI:3.20-17.07), and “fit/non-resilient” (OR=4.34, CI:2.16-8.71) phenotypes. Conclusions- Resilience is complementary to frailty in the identification of clinical phenotypes with different impact on wellness and QoL. Frailty and resilience should be evaluated in hospitalized COVID-19 patients to identify vulnerable individuals to prioritize urgent health interventions in people with PACS.

2023 - Sarcopenic Obesity Phenotypes in Patients With HIV: Implications for Cardiovascular Prevention and Rehabilitation [Articolo su rivista]
Milic, Jovana; Calza, Stefano; Cantergiani, Samuele; Albertini, Maddalena; Gallerani, Altea; Menozzi, Marianna; Barp, Nicole; Todisco, Vera; Renzetti, Stefano; Motta, Federico; Mussini, Cristina; Sebastiani, Giada; Raggi, Paolo; Guaraldi, Giovanni
abstract

Background: To describe prevalence, incidence and risk factors for sarcopenic obesity (SO) phenotypes in people living with HIV (PWH) and their association with subclinical cardiovascular disease (CVD). Methods: Observational, longitudinal study of PWH. A minimum of one criterion was necessary to diagnose sarcopenia: (i) weak hand grip (HG), (ii) low appendicular skeletal muscle index (ASMI), (iii) short physical performance battery (SPPB <11). Obesity was defined as (i) body mass index (BMI) ≥30 kg/m2 or (ii) visceral adipose tissue (VAT) ≥160 cm2. These variables combined generated five SO phenotypes: (i) severe SO: low HG+ low ASMI + low SPPB + high BMI; (ii) SO1: weak HG + high VAT; (iii) SO2: weak HG + high BMI; (iv) SO3: low ASMI + high VAT; (v) SO4: low ASMI + high BMI. Subclinical CVD was defined as carotid intima media thickness (IMT) ≥1 mm, presence of carotid plaque, or CAC score >10. Results: Among 2379 PWH 72% men, median age was 52 years, median HIV vintage 21 years, and median BMI 24 kg/m2. Two PWH had severe SO. The prevalence of SO1-SO4 was 19.7%, 3.6%, 20.8% and 0.8% respectively. Incidence of SO1-SO4 was 6.90, 1.2, 5.6 and 0.29 x 100 persons-year, respectively. SO1 was associated with risk of IMT ≥ 1, and SO3 with risk of CAC score >10. Conclusions: There was a large variability in incidence and prevalence of SO phenotypes. The presence of SO may have important implications for cardiovascular prevention and cardiac rehabilitation of PWH who suffered an event.

2023 - Successful living donor liver transplantation from an HIV and HCV positive donor: report from the first case in the world [Articolo su rivista]
Di Sandro, Stefano; Catellani, Barbara; Guidetti, Cristiano; Magistri, Paolo; Ballarin, Roberto; Pecchi, Annarita; Caracciolo, Daniela; Guaraldi, Giovanni; Guerrini, Gian Piero; Di Benedetto, Fabrizio
abstract

: HIV (human-immunodeficiency-virus) and HCV (hepatitis-C-virus) infections cause millions of deaths across the world every year. Since the introduction of effective therapies for HIV, in the middle of 1990 s, and HCV, after 2013, those two untreatable infections became completely controlled. Donor safety is the main goal in living donor liver transplantation (LDLT). An accurate pre-donation screening is mandatory for excluding risk factors related with any increase of donors' short-term and long-term morbidity. We present the first LDLT from a donor with both HIV and HCV previous infections. Donor and recipient did not experience any complication. Individuals with well controlled HIV/HCV infections and without any risk factors may be suitable for donation of a part of their healthy liver. An infographic is available for this article at:http://links.lww.com/QAD/C833.

2023 - The association of procalcitonin and C- reactive protein with bacterial infections acquired during ICU stay in COVID-19 critically ill patients. [Articolo su rivista]
Campani, Simone; Talamonti, Marta; Dall’Ara, Lorenzo; Coloretti, Irene; Gatto, Ilenia; Biagioni, Emanuela; Tosi, Martina; Meschiari, Marianna; Tonelli, Roberto; Clini, Enrico; Cossarizza, Andrea; Guaraldi, Giovanni; Mussini, Cristina; Sarti, Mario; Trenti, Tommaso; Girardis, Massimo
abstract

In COVID-19 patients, procalcitonin (PCT) and C-reactive protein (CRP) performance in identify-ing bacterial infections remains unclear. Our study aimed to evaluate the association of PCT and CRP with secondary infections acquired during ICU stay in critically ill COVID-19. This observa-tional study included adult patients admitted to three COVID-19 intensive care units (ICU) from February 2020 to May 2022 with respiratory failure caused by SARS-CoV-2 infection and ICU stay≥ 11 days. The values of PCT and CRP collected on the day of infection diagnosis were com-pared to those collected on day 11 after ICU admission, the median time for infection occurrence, in patients without secondary infection. The receiver operating characteristic curve (ROC) and multivariate logistic model were used to assess PCT and CRP association with secondary infec-tions. Two hundred and seventy-nine patients were included, of whom 169 (60,6%) developed secondary infection after ICU admission. The PCT and CRP values observed on the day of the in-fection diagnosis were larger (p< 0,001) than those observed on day 11 after ICU admission in pa-tients without secondary infections. The ROC analysis calculated an AUC of 0,744 (95%CI 0,685-0,803) and 0,754 (95%CI 0,695-0,812) for PCT and CRP, respectively. Multivariate logistic models showed that PCT ≥ 0,16 ng/ml and CRP≥ 1,35 mg/dl were associated (p<0,001) with infections acquired during ICU stay. Our results indicated that PCT and CRP values were associated with developing secondary infections in COVID-19 patients with an ICU stay > 11 days with an ac-ceptable level of diagnostic accuracy using cut-off values lower than those commonly used in no-COVID-19 patients.

2023 - Vancomycin resistant enterococcus risk factors for hospital colonization in hematological patients: a matched case-control study [Articolo su rivista]
Meschiari, Marianna; Kaleci, Shaniko; Monte, Martina Del; Dessilani, Andrea; Santoro, Antonella; Scialpi, Francesco; Franceschini, Erica; Orlando, Gabriella; Cervo, Adriana; Monica, Morselli; Forghieri, Fabio; Venturelli, Claudia; Ricchizzi, Enrico; Chester, Johanna; Sarti, Mario; Guaraldi, Giovanni; Luppi, Mario; Mussini, Cristina
abstract

BackgroundVancomycin-resistant enterococcus (VRE) was the fastest growing pathogen in Europe in 2022 (+ 21%) but its clinical relevance is still unclear. We aim to identify risk factors for acquired VRE rectal colonization in hematological patients and evaluate the clinical impact of VRE colonization on subsequent infection, and 30- and 90-day overall mortality rates, compared to a matched control group.MethodsA retrospective, single center, case-control matched study (ratio 1:1) was conducted in a hematological department from January 2017 to December 2020. Case patients with nosocomial isolation of VRE from rectal swab screening (>= 48 h) were matched to controls by age, sex, ethnicity, and hematologic disease. Univariate and multivariate logistic regression compared risk factors for colonization.ResultsA total of 83 cases were matched with 83 controls. Risk factors for VRE colonization were febrile neutropenia, bone marrow transplant, central venous catheter, bedsores, reduced mobility, altered bowel habits, cachexia, previous hospitalization and antibiotic treatments before and during hospitalization. VRE bacteraemia and Clostridioides difficile infection (CDI) occurred more frequently among cases without any impact on 30 and 90-days overall mortality. Vancomycin administration and altered bowel habits were the only independent risk factors for VRE colonization at multivariate analysis (OR: 3.53 and 3.1; respectively).ConclusionsAntimicrobial stewardship strategies to reduce inappropriate Gram-positive coverage in hematological patients is urgently required, as independent risk factors for VRE nosocomial colonization identified in this study include any use of vancomycin and altered bowel habits. VRE colonization and infection did not influence 30- and 90-day mortality. There was a strong correlation between CDI and VRE, which deserves further investigation to target new therapeutic approaches.

2023 - Why we need to re-define long-term success for people living with HIV [Articolo su rivista]
Fuster-RuizdeApodaca, Maria J; Wohl, David A; Cascio, Mario; Guaraldi, Giovanni; Rockstroh, Jürgen; Hodson, Matthew; Richman, Bruce; Brown, Gina; Anderson, Jane; Lazarus, Jeffrey V
abstract

: Over the past few decades, the life expectancy of people living with HIV has markedly improved due to the advances in HIV diagnosis, linkage to care, and treatment. However, with these advances, a new set of challenges has emerged that must be addressed to ensure the long-term well-being of people living with HIV. In this article, as part of a wider journal supplement, we explore the unmet needs and challenges across the HIV continuum of care and re-define what long-term success looks like to support the healthy ageing of all people affected by HIV.

2022 - A Machine learning approach to predict Weight change in ART experienced PLWH [Esposizione]
Motta, Federico; Milić, Jovana; Barbieri, Sara; Gozzi, Licia; Aprile, Emanuele; Belli, Michela; Venuta, Maria; Cuomo, Gianluca; Carli, Federica; Dolci, Giovanni; Iadisernia, Vittorio; Burastero, Giulia; Mussini, Cristina; Mandreoli, Federica; Guaraldi, Giovanni
abstract

2022 - A proof-of-concept study on the genomic evolution of Sars-Cov-2 in molnupiravir-treated, paxlovid-treated and drug-naïve patients [Articolo su rivista]
Alteri, Claudia; Fox, Valeria; Scutari, Rossana; Burastero, Giulia Jole; Volpi, Sara; Faltoni, Matteo; Fini, Vanessa; Granaglia, Annarita; Esperti, Sara; Gallerani, Altea; Costabile, Valentino; Fontana, Beatrice; Franceschini, Erica; Meschiari, Marianna; Campana, Andrea; Bernardi, Stefania; Villani, Alberto; Bernaschi, Paola; Russo, Cristina; Guaraldi, Giovanni; Mussini, Cristina; Perno, Carlo Federico
abstract

Little is known about SARS-CoV-2 evolution under Molnupiravir and Paxlovid, the only antivirals approved for COVID-19 treatment. By investigating SARS-CoV-2 variability in 8 Molnupiravir-treated, 7 Paxlovid-treated and 5 drug-naive individuals at 4 time-points (Days 0-2-5-7), a higher genetic distance is found under Molnupiravir pressure compared to Paxlovid and no-drug pressure (nucleotide-substitutions/site mean & PLUSMN;Standard error: 18.7 x 10(-4) & PLUSMN; 2.1 x 10(-4) vs. 3.3 x 10(-4) & PLUSMN; 0.8 x 10(-4) vs. 3.1 x 10(-4) & PLUSMN; 0.8 x 10(-4), P = 0.0003), peaking between Day 2 and 5. Molnupiravir drives the emergence of more G-A and C-T transitions than other mutations (P = 0.031). SARS-CoV-2 selective evolution under Molnupiravir pressure does not differ from that under Paxlovid or no-drug pressure, except for orf8 (dN > dS, P = 0.001); few amino acid mutations are enriched at specific sites. No RNA-dependent RNA polymerase (RdRp) or main proteases (Mpro) mutations conferring resistance to Molnupiravir or Paxlovid are found. This proof-of-concept study defines the SARS-CoV-2 within-host evolution during antiviral treatment, confirming higher in vivo variability induced by Molnupiravir compared to Paxlovid and drug-naive, albeit not resulting in apparent mutation selection.

2022 - Acid base disorders in patients with COVID-19 [Articolo su rivista]
Alfano, Gaetano; Fontana, Francesco; Mori, Giacomo; Giaroni, Francesco; Ferrari, Annachiara; Giovanella, Silvia; Ligabue, Giulia; Ascione, Elisabetta; Cazzato, Silvia; Ballestri, Marco; Di Gaetano, Margherita; Meschiari, Marianna; Menozzi, Marianna; Milic, Jovana; Andrea, Bedini; Franceschini, Erica; Cuomo, Gianluca; Magistroni, Riccardo; Mussini, Cristina; Cappelli, Gianni; Guaraldi, Giovanni; De Biasi, Sara; Cossarizza, Andrea; Gibellini, Lara
abstract

Purpose Acid-base derangement has been poorly described in patients with coronavirus disease 2019 (COVID-19). Considering the high prevalence of pneumonia and kidneys injury in COVID-19, frequent acid-base alterations are expected in patients admitted with SARS-Cov-2 infection. The study aimed to assess the prevalence of acid-base disorders in symptomatic patients with a diagnosis of COVID-19. Methods The retrospective study enrolled COVID-19 patients hospitalized at the University Hospital of Modena from 4 March to 20 June 2020. Baseline arterial blood gas (ABG) analysis was collected in 211 patients. In subjects with multiple ABG analysis, we selected only the first measurement. A pH of less than 7.37 was categorized as acidemia and a pH of more than 7.43 was categorized as alkalemia. Results ABG analyses revealed a low arterial partial pressure of oxygen (PO2, 70.2 +/- 25.1 mmHg), oxygen saturation (SO2, 92%) and a mild reduction of PO2/FiO(2) ratio (231 +/- 129). Acid-base alterations were found in 79.7% of the patient. Metabolic alkalosis (33.6%) was the main alteration followed by respiratory alkalosis (30.3%), combined alkalosis (9.4%), respiratory acidosis (3.3%), metabolic acidosis (2.8%) and other compensated acid-base disturbances (3.6%). All six patients with metabolic acidosis died at the end of the follow-up. Conclusion Variations of pH occurred in the majority (79.7%) of patients admitted with COVID-19. The patients experienced all the type of acid-base disorders, notably metabolic and respiratory alkalosis were the most common alterations in this group of patients.

2022 - Association between respiratory distress time and invasive mechanical ventilation in COVID-19 patients: a multicentre regional cohort study. [Articolo su rivista]
Busani, Stefano; Coloretti, Irene; Baciarello, Marco; Bellini, Valentina; Sarti, Marco; Biagioni, Emanuela; Tonelli, Roberto; Marchioni, Alessandro; Clini, Enrico; Guaraldi, Giovanni; Mussini, Cristina; Meschiari, Marianna; Tonetti, Tommaso; Pisani, Lara; Nava, Stefano; Bignami, Elena; Ranieri, Marco; Girardis, Massimo
abstract

Aim: to determine whether the duration of respiratory distress symptoms in severe COVID-19 pneumonia affects the need for invasive mechanical ventilation and clinical outcomes. Materials and methods: an observational multicentre cohort study of patients hospitalised in five COVID-19–designated ICUs of the University Hospitals of Emilia-Romagna Region. Patients included were adults with pneumonia due to SARS-CoV-2 with PaO₂/FiO₂ ratio <300 mmHg, respiratory distress symptoms, and need for mechanical ventilation (invasive or non-invasive). Exclusion criteria were an uncertain time of respiratory distress, end-of-life decision, and mechanical respiratory support before hospital admission. Measurements and main results: we analysed 171 patients stratified into tertiles according to respiratory distress duration (distress time, DT) before application of mechanical ventilation support. The rate of patients requiring invasive mechanical ventilation was significantly different (p<0.001) among the tertiles: 17/57 patients in the shortest duration, 29/57 in the intermediate duration, and 40/57 in the longest duration. The respiratory distress time significantly increased the risk of invasive ventilation in the univariate analysis (OR 5.5 [CI 2.48–12.35], p = 0.003). Multivariable regression analysis confirmed this association (OR 10.7 [CI 2.89–39.41], p <0.001). Clinical outcomes (mortality and hospital stay) did not show significant differences between DT tertiles. Discussion: albeit preliminary and retrospective, our data raised the hypothesis that the duration of respiratory distress symptoms may play a role in COVID-19 patients’ need for invasive mechanical ventilation. Furthermore, our observations suggested that specific strategies may be directed towards identifying and managing early symptoms of respiratory distress, regardless of the levels of hypoxemia and the severity of the dyspnoea itself.

2022 - Atherogenicity of low-density lipoproteins after switching from a protease inhibitor to dolutegravir: a substudy of the NEAT022 study [Articolo su rivista]
Saumoy, Maria; Sánchez-Quesada, Jose Luís; Assoumou, Lambert; Gatell, José Maria; González-Cordón, Ana; Guaraldi, Giovanni; Domingo, Pere; Giacomelli, Andrea; Connault, Jérôme; Katlama, Christine; Masiá, Mar; Ordónez-Llanos, Jordi; Pozniak, Anton; Martínez, Esteban; Podzamczer, Daniel
abstract

Background The aim of this study was to investigate whether switching from a ritonavir-boosted PI-based regimen to a dolutegravir-based regimen improved the atherogenic properties of LDL particles in patients with HIV. Methods This was a substudy of the NEAT022 study (ClinicalTrials.gov NCT02098837). Adults with HIV with a Framingham score >10% or aged >50 years and being treated with a stable boosted PI-based regimen were randomized to either switch to dolutegravir or continue with boosted PI. At baseline and Week 48, we assessed atherogenic LDL properties: LDL particle size and phenotype (A, intermediate, B), oxidized LDL (ox-LDL) and lipoprotein-associated phospholipase A2 (Lp-PLA2) activity. Results Eighty-six participants (dolutegravir 44; PI 42) were included. Participants had a median (IQR) age of 54 (51-57) years and 79.1% were male. In the dolutegravir arm, after 48 weeks, we observed: (1) an increase in LDL size [median 1.65 angstrom (IQR -0.60 to 4.20); P = 0.007], correlated with the decrease in triglyceride concentration [Spearman correlation = -0.352 (P = 0.001)], with a corresponding decrease of subjects with atherogenic LDL phenotype B (36.4% to 20.5%; P = 0.039); (2) a decrease in Lp-PLA2 activity [median 1.39 mu mol/min/mL (IQR -2.3 to 0.54); P = 0.002]; and (3) a decrease in ox-LDL [median 14 U/L (IQR -102 to 13); P = 0.006]. In the PI arm, none of these favourable lipid modifications was observed. Conclusions Forty-eight weeks after switching from a PI-based to a dolutegravir-based regimen, patients with Framingham score >10% or aged >50 years showed improvement of several atherogenic lipid features, including LDL particle phenotype, ox-LDL and Lp-PLA2.

2022 - Awaiting a cure for COVID-19: therapeutic approach in patients with different severity levels of COVID-19 [Articolo su rivista]
Alfano, G.; Morisi, N.; Frisina, M.; Ferrari, A.; Fontana, F.; Tonelli, R.; Franceschini, E.; Meschiari, M.; Donati, G.; Guaraldi, G.
abstract

COVID-19 is an unpredictable infectious disease caused by SARS-CoV-2. The development of effective anti-COVID-19 vaccines has enormously minimized the risk of severe illness in most immunocompetent patients. However, unvaccinated patients and non-re-sponders to the COVID-19 vaccine are at risk of short-and long-term consequences. In these patients, the outcome of COVID-19 relies on an interplay of multiple factors including age, immunocompetence, comorbid-ities, inflammatory response triggered by the virus as well as the virulence of SARS-CoV-2 variants. General-ly, COVID-19 is asymptomatic or mildly symptomatic in young people, but it may manifest with respiratory insufficiency requiring mechanical ventilation in cer-tain susceptible groups of patients. Furthermore, severe SARS-CoV-2 infection induces multiorgan failure syndrome by affecting liver, kidney heart and nervous system. Since December 2019, multiple drugs have been test-ed to treat COVID-19, but only a few have been prov-en effective to mitigate the course of the disease that continues to cause death and comorbidity worldwide. Current treatment of COVID-19 patients is essential-ly based on the administration of supportive oxygen therapy and the use of specific drugs such as steroids, anticoagulants, antivirals, anti-SARS-CoV-2 antibodies and immunomodulators. However, the rapid spread of new variants and the release of new data coming from the numerous ongoing clinical trials have cre-ated the conditions for maintaining a continuous up-dating of the therapeutic management of COVID-19 patients. Furthermore, we believe that a well-estab-lished therapeutic strategy along with the continu-um of medical care for all patients with COVID-19 is pivotal to improving disease outcomes and restoring healthcare care fragmentation caused by the pandem-ic. This narrative review, focusing on the therapeutic management of COVID-19 patients, aimed to provide an overview of current therapies for (i) asymptomatic or mildly/moderate symptomatic patients, (ii) hospitalized patients requiring low-flow oxygen, (iii) high-flow oxygen and (iv) mechanical ventilation.

2022 - Characteristics of long COVID among older adults: a cross-sectional study [Articolo su rivista]
Daitch, Vered; Yelin, Dana; Awwad, Muhammad; Guaraldi, Giovanni; Milić, Jovana; Mussini, Cristina; Falcone, Marco; Tiseo, Giusy; Carrozzi, Laura; Pistelli, Francesco; Nehme, Mayssam; Guessous, Idris; Kaiser, Laurent; Vetter, Pauline; Bordas-Martínez, Jaume; Durà-Miralles, Xavier; Peleato-Catalan, Dolores; Gudiol, Carlota; Shapira-Lichter, Irit; Abecasis, Donna; Leibovici, Leonard; Yahav, Dafna; Margalit, Ili
abstract

To describe long-COVID symptoms among older adults, and to assess risk factors for two common long-COVID symptoms: fatigue and dyspnea.

2022 - Clinical recrudescence of chronic untreated P. malariae infection after BNT162b2 CoVID-19 vaccine [Articolo su rivista]
Ciusa, G.; Guida Marascia, F.; Virruso, R.; Angheben, A.; Guaraldi, G.; Cascio, A.
abstract

We described a case of clinical reactivation of chronic P. malariae infection following CoVID-19 vaccination with BNT162b2 (Pifzer-Biontech CoVID-19 vaccine) in a 48-year old Italian man.The patient came to our attention for fever of unknown origin show a quartan pattern (every third day) associated to splenomegaly, the onset of the fever occurred one month after CoVID-19 vaccination with BNT162b2. P. malariae was diagnosed using Carestart™ malaria rapid test and Polymerase-Chain Reaction. Post-vaccine transient reduction of immune reactivity is described in literature, although the mechanism is unknown.

2022 - Contribution of integrase inhibitor use, body mass index, physical activity and caloric intake to weight gain in people living with HIV [Articolo su rivista]
Guaraldi, Giovanni; Milic, Jovana; Bacchi, Elena; Carli, Federica; Menozzi, Marianna; Franconi, Iacopo; Raimondi, Alessandro; Ciusa, Giacomo; Masi, Valentina; Belli, Michela; Guaraldi, Stefano; Aprile, Emanuele; Mancini, Maria; Mussini, Cristina; Lake, Jordan E; Erlandson, Kristine M
abstract

: Background: Integrase inhibitor (INSTI) use has been associated with greater weight gain (WG) among people living with HIV (PLWH), but it is unclear how this effect compares in magnitude to traditional risk factors for WG. We assessed the population attributable fractions (PAFs) of modifiable lifestyle factors and INSTI regimens in PLWH who experienced a ≥5% WG over follow-up. Methods: In an observational cohort study from 2007 to 2019 at Modena HIV Metabolic Clinic, Italy, ART-experienced but INSTI-naive PLWH were grouped as INSTI-switchers vs non-INSTI. Groups were matched for sex, age, baseline BMI and follow-up duration. Significant WG was defined as an increase of ≥5% from 1st visit weight over follow-up. PAFs and 95% CIs were estimated to quantify the proportion of the outcome that could be avoided if the risk factors were not present. Results: 118 PLWH switched to INSTI and 163 remained on current ART. Of 281 PLWH (74.3% males), mean follow-up was 4.2 years, age 50.3 years, median time since HIV diagnosis 17.8 years, CD4 cell count 630 cells/µL at baseline. PAF for weight gain was the greatest for high BMI (45%, 95% CI: 27-59, p < 0.001), followed by high CD4/CD8 ratio (41%, 21-57, p < 0.001) and lower physical activity (32%, 95% CI 5-52, p = 0.03). PAF was not significant for daily caloric intake (-1%, -9-13, p = 0.45), smoking cessation during follow-up (5%, 0-12, p = 0.10), INSTI switch (11%, -19-36; p = 0.34). Conclusions: WG in PLWH on ART is mostly influenced by pre-existing weight and low physical activity, rather than switch to INSTI.

2022 - Correlates of Treatment and Disease Burden in People Living with HIV (PLHIV) in Italy [Articolo su rivista]
Cingolani, A.; Tavelli, A.; Maggiolo, F.; Perziano, A.; Saracino, A.; Vichi, F.; Cernuschi, M.; Guaraldi, G.; Quiros-Roldan, E.; Castagna, A.; Antinori, A.; Monforte, A. D.
abstract

Treatment burden is a multidimensional concept, including several aspects of life of patients affected by chronic conditions. It has been poorly explored in people living with HIV (PLHIV). An online anonymous survey of PLHIV taking antiretroviral therapy (ART) was conducted, in order to investigate the self-reported correlates of disease burden. HIV Treatment and Diseases Burden (TDB) was investigated with a questionnaire containing 31 items in 7 domains. Respondents were stratified in high burden (H-TDB)/low burden (L-TDB) according to overall HIV TDB mean + 1 standard deviation. Factors associated with H-TDB has been evaluated with a logistic regression model. In total, 531 PLHIV completed the questionnaire. 99 PLHIV had a H-TDB (18.6%). PLHIV with H-TDB were younger (p < 0.001), less frequently on current two drug antiretroviral (ARV) regimens (p = 0.01) and more frequently with plasma HIV-RNA >50 copies/mL (p = 0.04). At multivariable regression analysis, younger age (aOR 1.43, 95%CI 1.14–1.80; p = 0.002), not fully treatment satisfaction (aOR 2.19, 95%CI 1.28–3.74; p = 0.004), the need of a more accurate dialogue with treating physician (aOR 2.29, 95%CI 1.21–4.36, p = 0.01) and a self-declared lower overall Health Status (aOR 1.75, 95%CI 1.33–2.32; p = 0.002) were all associated with a H-TDB. One out of five PLHIV showed a high level of treatment and disease burden. Younger age, not fully satisfaction with ART and need of interaction with a tailored health system should be taken into consideration as correlates of treatment and disease burden in a patient-centered approach, to reduce the negative impact that it can produce on the overall perceived health status of the person.

2022 - Cytomegalovirus blood reactivation in COVID-19 critically ill patients: risk factors and impact on mortality. [Articolo su rivista]
Gatto, Ilenia; Biagioni, Emanuela; Coloretti, Irene; Farinelli, Carlotta; Avoni, Camilla; Caciagli, Valeria; Busani, Stefano; Sarti, Mario; Pecorari, Monica; Gennari, William; Guaraldi, Giovanni; Franceschini, Erica; Meschiari, Marianna; Mussini, Cristina; Tonelli, Roberto; Clini, Enrico; Cossarizza, Andrea; Girardis, Massimo; Gibellini, Lara
abstract

Purpose: Cytomegalovirus (CMV) reactivation in immunocompetent critically ill patients is common and relates to a worsening outcome. In this large observational study, we evaluated the incidence and the risk factors associated with CMV reactivation and its effects on mortality in a large cohort of COVID-19 patients admitted to the intensive care unit (ICU). Methods: Consecutive patients with confirmed SARS-CoV-2 infection and acute respiratory distress syndrome admitted to three ICUs from February 2020 to July 2021 were included. The patients were screened at ICU admission and once or twice per week for quantitative CMV-DNAemia in the blood. The risk factors associated with CMV blood reactivation and its association with mortality were estimated by adjusted Cox proportional hazards regression models. Results: CMV blood reactivation was observed in 88 patients (20,4%) of the 431 patients studied. SAPS II score (HR 1,031, 95% CI 1,010-1,053, p=0,006), platelet count (HR 0,0996, 95% CI 0,993-0,999, p=0,004), invasive mechanical ventilation (HR 2,611, 95% CI 1,223-5,571, p=0,013) and secondary bacterial infection (HR 5,041; 95% CI 2,852-8,911, p<0,0001) during ICU stay were related to CMV reactivation. Hospital mortality was higher in patients with (67,0%) than in patients without (24,5%) CMV reactivation but the adjusted analysis did not confirm this association (HR 1,141, 95% CI 0,757-1,721, p=0,528). Conclusion: The severity of illness and the occurrence of secondary bacterial infections were associated with an increased risk of CMV blood reactivation, which, however, does not seem to influence the outcome of COVID-19 ICU patients independently.

2022 - “Dangerous liaisons: NAFLD and liver fibrosis increase cardiovascular risk in HIV” [Articolo su rivista]
Cervo, A.; Sebastiani, G.; Milic, J.; Krahn, T.; Mazzola, S.; Petta, S.; Cascio, A.; Guaraldi, G.; Mazzola, G.
abstract

Objectives: Non-alcoholic fatty liver disease (NAFLD) is strongly associated with cardiovascular disease in the general population. We aimed to assess the impact of NAFLD and liver fibrosis on intermediate-high cardiovascular risk in people living with HIV. Methods: We included people living with HIV from three cohorts. NAFLD and significant liver fibrosis were defined using transient elastography: controlled attenuation parameter ≥288 dB/m and liver stiffness measurement ≥7.1 kPa, respectively. Cardiovascular risk was assessed with the atherosclerotic cardiovascular disease (ASCVD) risk estimator in patients aged between 40 and 75 years and categorised as low if <5%, borderline if 5%–7.4%, intermediate if 7.5%–19.9% and high if ≥20% or with the presence of a previous cardiovascular event. Patients with hepatitis B and/or hepatitis C virus co-infection, alcohol abuse and unreliable transient elastography measurements were excluded. Predictors of intermediate-high cardiovascular risk were investigated in multivariable analysis by logistic regression and also by stratifying according to body mass index (BMI; cut-offs of 25 and 30 kg/m2) and age (cut-off of 60 years). Results: Of 941 patients with HIV alone included, 423 (45%), 128 (13.6%), 260 (27.6%) and 130 (13.8%) were categorised as at low, borderline, intermediate and high ASCVD risk, respectively. Predictors of intermediate-high ASCVD risk were NAFLD (adjusted odds ratio [aOR] 2.11; 95% confidence interval [CI] 1.40–3.18; p < 0.001), liver fibrosis (aOR 1.64; 95% CI 1.03–2.59; p = 0.034), duration of HIV (aOR 1.04; 95% CI 1.02–1.06; p < 0.001), and previous exposure to thymidine analogues and/or didanosine (aOR 1.54; 95% CI 1.09–2.18; p = 0.014). NAFLD was also associated with higher cardiovascular risk in normoweight patients (aOR 2.97; 95% CI 1.43–6.16; p = 0.003), in those with BMI <30 kg/m2 (aOR 2.30; 95% CI 1.46–3.61; p < 0.001) and in those aged <60 years (aOR 2.19; 95% CI 1.36–3.54; p = 0.001). Conclusion: Assessment of cardiovascular disease should be targeted in people living with HIV with NAFLD and/or significant liver fibrosis, even if they are normoweight and young.

2022 - Decay pattern of anti–SARS–CoV–2 antibodies in PWH [Abstract in Atti di Convegno]
Milić, Jovana; Tili, Alessandro; Renzetti, Stefano; Motta, Federico; Meschiari, Marianna; Fogliani, Rossella; Ferrari, Filippo; Meccugni, Barbara; Mimmi, Stefano; Borsari, Silvana; Calza, Stefano; Cossarizza, Andrea; Mussini, Cristina; Guaraldi, Giovanni
abstract

2022 - Diagnosis of liver fibrosis in ageing patients with HIV at risk for non-alcoholic fatty liver disease in Italy and Canada: assessment of a two-tier pathway [Articolo su rivista]
Sebastiani, Giada; Milic, Jovana; Gioe, Claudia; Al Hinai, Al Shaima; Cervo, Adriana; Lebouche, Bertrand; Deschenes, Marc; Cascio, Antonio; Mazzola, Giovanni; Guaraldi, Giovanni
abstract

Background: Since the introduction of effective antiretroviral therapy, liver-related mortality has increased ten-fold in ageing people with HIV. This trend is driven by ageing-related metabolic conditions that cause non-alcoholic fatty liver disease (NAFLD), which affects 35-65% of people with HIV. Clinically significant (stage 2-4) liver fibrosis develops in over 15% of people with HIV who have NAFLD. Strategies are needed to identify people with HIV at risk for significant liver fibrosis and reduce cirrhosis-related complications. Non-invasive tests to diagnose liver fibrosis include ultrasound-based transient elastography and serum biomarkers. Transient elastography is a feasible tool to assess liver fibrosis, but it is not largely accessible in HIV clinics. We aimed to determine whether a two-tier care pathway with assessment of simple serum biomarkers for fibrosis as first tier could reduce the need for the specialist transient elastography test (second tier). Methods: Patients were consecutively identified through a clinical programme for liver disease in people with HIV in Canada and Italy. We applied a two-tier care pathway to three prospective cohorts of people with HIV at risk for NAFLD, defined as those with elevated liver transaminases, body mass index (BMI) of 25 or greater, or diabetes. Patients with alcohol abuse or coinfection with hepatitis B or C viruses were excluded. Five simple serum biomarkers of fibrosis, based on liver transaminases, platelets, and BMI (fibrosis-4 index [FIB-4], BARD [BMI, AST to ALT ratio, diabetes] score, NAFLD fibrosis score, AST to ALT ratio, and AST-to-platelet ratio index [APRI]) were applied as a first-tier assessment to exclude significant liver fibrosis. All patients then received transient elastography. We assessed the decrease in referral for transient elastography that would have occurred based on biomarker assessment and discordance between high transient elastography (≥7·1 kPa), indicating significant liver fibrosis, and low serum fibrosis biomarkers (FIB-4 <1·3, BARD score 0-1, NAFLD fibrosis score less than -1·455, AST to ALT ratio <0·8, and APRI <0·5). We also assessed independent factors associated with that discordance by multivariable logistic regression analysis. Findings: We included 1202 people with HIV at risk for NAFLD (mean age 51·2 years [SD 10·1], 914 [76%] male and 288 [24%] female, mean HIV duration 16·3 years [SE 9·7], mean BMI 26·5 Kg/m2 [SD 4·5]; prevalence of diabetes 49·5%). 222 (18·5%) of these participants had significant liver fibrosis according to transient elastography. Assessment of simple fibrosis biomarkers would have decreased transient elastography referrals between 22·5% (BARD score) and 82·4% (APRI). Discordance rate ranged from 3·9% (NAFLD fibrosis score) to 11·1% (APRI). After adjustment for age, sex, presence of diabetes, level of HDL cholesterol, and CD4 cell count, BMI (odds ratio 1·12, 95% CI 1·07-1·17) and triglyceride level (1·25, 1·08-1·46) were independent predictors of discordance for low APRI and high transient elastography. Interpretation: Use of a two-tier pathway to identify liver fibrosis in ageing people with HIV at risk for NAFLD could reduce transient elastography examinations by a substantial proportion, reducing costs and helping to optimise use of resources in HIV care.

2022 - First and second wave among hospitalized COVID-19 patients with severe pneumonia: a comparison of 28-day mortality over 1-year pandemic in a tertiary university hospital in Italy. [Articolo su rivista]
Meschiari, M; Cozzi-Lepri, A; Tonelli, R; Bacca, E; Menozzi, M; Franceschini, E; Cuomo, G; Bedini, A; Volpi, S; Milic, J; Brugioni, L; Romagnoli, E; Pietrangelo, A; Corradini, E; Coloretti, I; Biagioni, E; Busani, S; Girardis, M; Cossarizza, A; Clini, E; Guaraldi, G; Mussini, C.
abstract

Objectives: The first COVID-19-19 epidemic wave was over the period February-May 2020. Since October 1st, 2020 Italy, as many other European countries, faced a second wave. The aim of this analysis was to compare the 28-day mortality between the two waves among COVID-19 hospitalised patients. Design: Observational cohort study. Standard survival analysis was performed to compare all-cause mortality within 28 days after hospital admission in the two waves. Kaplan-Meier curves as well as Cox regression model analysis were used. The effect of wave on risk of death was shown by means of hazard ratios (HRs) with 95% confidence intervals (CI). A sensitivity analysis around the impact of the circulating variant as a potential unmeasured confounder was performed. Setting: University Hospital of Modena, Italy. Patients admitted to hospital for severe COVID-19 pneumonia during the first (February 22nd – May 31st, 2020) and second wave (October 1st- December 31st, 2020) were included. Results: During the two study periods, a total of 1,472 patients with severe COVID-19 pneumonia were admitted to our hospital, 449 during the first wave and 1,023 during the second. Median age was 70 years (IQR:56-80), 37% females, 49% with PaO /FiO < 250 mmHg, 82% with ≥1 comorbidity, median duration of symptoms was 6 days. 28-day mortality rate was 20.0% (95% CI:16.3-23.7) during the first wave vs. 14.2% (95% CI:12.0-16.3) in the second (log-rank test p-value= 0.03). After including key predictors of death in the multivariable Cox regression model, the data still strongly suggested a lower 28-day mortality rate in the 2nd wave (aHR=0.64, 95% CI: 0.45, 0.90, p- value=0.01). Conclusions: In our hospitalized COVID-19 patients with severe pneumonia, the 28-day mortality appeared to be reduced by 36% during the second as compared to the first wave. Further studies are needed to identify factors that may have contributed to this improved survival.

2022 - Frailty in older people living with HIV: current status and clinical management [Articolo su rivista]
Kehler, D Scott; Milic, Jovana; Guaraldi, Giovanni; Fulop, Tamas; Falutz, Julian
abstract

This paper will update care providers on the clinical and scientific aspects of frailty which affects an increasing proportion of older people living with HIV (PLWH). The successful use of combination antiretroviral therapy has improved long-term survival in PLWH. This has increased the proportion of PLWH older than 50 to more than 50% of the HIV population. Concurrently, there has been an increase in the premature development of age-related comorbidities as well as geriatric syndromes, especially frailty, which affects an important minority of older PLWH. As the number of frail older PLWH increases, this will have an important impact on their health care delivery. Frailty negatively affects a PLWH's clinical status, and increases their risk of adverse outcomes, impacting quality of life and health-span. The biologic constructs underlying the development of frailty integrate interrelated pathways which are affected by the process of aging and those factors which accelerate aging. The negative impact of sarcopenia in maintaining musculoskeletal integrity and thereby functional status may represent a bidirectional interaction with frailty in PLWH. Furthermore, there is a growing body of literature that frailty states may be transitional. The recognition and management of related risk factors will help to mitigate the development of frailty. The application of interdisciplinary geriatric management principles to the care of older PLWH allows reliable screening and care practices for frailty. Insight into frailty, increasingly recognized as an important marker of biologic age, will help to understand the diversity of clinical status occurring in PLWH, which therefore represents a fundamentally new and important aspect to be evaluated in their health care.

2022 - From NAFLD to MAFLD: implications of change in terminology in PWH [Abstract in Atti di Convegno]
Gozzi, Licia; Milić, Jovana; Renzetti, Stefano; Motta, Federico; Cervo, Adriana; Burastero, Giulia; Iadisernia, Vittorio; Lebouche, Bertrand; Al Hinai, Shaima; Deschenes, Marc; Menozzi, Marianna; Raggi, Paolo; Calza, Stefano; Mussini, Cristina; Sebastiani, Giada; Guaraldi, Giovanni
abstract

2022 - From NAFLD to MAFLD: implications of change in terminology in PWH [Abstract in Atti di Convegno]
Guaraldi, Giovanni; Milić, Jovana; Renzetti, Stefano; Motta, Federico; Gozzi, Licia; Cervo, Adriana; Burastero, Giulia; Iadisernia, Vittorio; Lebouché, Bertrand; Al Hinai, Shaima; Deschenes, Marc; Raggi, Paolo; Calza, Stefano; Mussini, Cristina; Sebastiani, Giada
abstract

2022 - HCV reinfection after HCV therapy among HIV/HCV-coinfected individuals in Europe [Articolo su rivista]
Amele, S.; Sandri, A. K.; Rodger, A.; Vandekerckhove, L.; Benfield, T.; Milinkovic, A.; Duvivier, C.; Stellbrink, H. -J.; Sambatakou, H.; Chkhartishvili, N.; Caldeira, L.; Laguno, M.; Domingo, P.; Wandeler, G.; Gisinger, M.; Kuzovatova, E.; Dragovic, G.; Knysz, B.; Matulionyte, R.; Rockstroh, J. K.; Lundgren, J. D.; Mocroft, A.; Peters, L.; Harxhi, A.; Losso, M.; Kundro, M.; Schmied, B.; Zangerle, R.; Karpov, I.; Vassilenko, A.; Mitsura, V. M.; Paduto, D.; Clumeck, N.; Wit, S. D.; Delforge, M.; Florence, E.; Vandekerckhove, L.; Hadziosmanovic, V.; Begovac, J.; Machala, L.; Jilich, D.; Sedlacek, D.; Kronborg, G.; Benfield, T.; Gerstoft, J.; Katzenstein, T.; Pedersen, C.; Johansen, I. S.; Ostergaard, L.; Wiese, L.; Moller, N. F.; Nielsen, L. N.; Zilmer, K.; Smidt, J.; Aho, I.; Viard, J. -P.; Girard, P. -M.; Pradier, C.; Fontas, E.; Duvivier, C.; Rockstroh, J.; Behrens, G.; Degen, O.; Stellbrink, H. J.; Stefan, C.; Bogner, J.; Fatkenheuer, G.; Chkhartishvili, N.; Sambatakou, H.; Adamis, G.; Paissios, N.; Szlavik, J.; Gottfredsson, M.; Devitt, E.; Tau, L.; Turner, D.; Burke, M.; Shahar, E.; Hassoun, G.; Elinav, H.; Haouzi, M.; Elbirt, D.; D'Arminio Monforte, A.; Esposito, R.; Mazeu, I.; Mussini, C.; Mazzotta, F.; Gabbuti, A.; Lazzarin, A.; Castagna, A.; Gianotti, N.; Galli, M.; Ridolfo, A.; Sacco, L.; Uzdaviniene, V.; Matulionyte, R.; Staub, T.; Hemmer, R.; Dragas, S.; Stevanovic, M.; Reiss, P.; Trajanovska, J.; Reikvam, D. H.; Maeland, A.; Bruun, J.; Knysz, B.; Gasiorowski, J.; Inglot, M.; Bakowska, E.; Flisiak, R.; Grzeszczuk, A.; Parczewski, M.; Maciejewska, K.; Aksak-Was, B.; Beniowski, M.; Mularska, E.; Jablonowska, E.; Kamerys, J.; Wojcik, K.; Mozer-Lisewska, I.; Rozplochowski, B.; Zagalo, A.; Mansinho, K.; Maltez, F.; Radoi, R.; Oprea, C.; Davila, C.; Yakovlev, A.; Trofimora, T.; Khromova, I.; Kuzovatova, E.; Blokhina, I. N.; Novogrod, N.; Borodulina, E.; Vdoushkina, E.; Ranin, J.; Tomazic, J.; Miro, J. M.; Miro, J. M.; Martinez, E.; Garcia, F.; Blanco, J. L.; Martinez-Rebollar, M.; Mallolas, J.; Callau, P.; Rojas, J.; Inciarta, A.; Moreno, S.; del Campo, S.; Clotet, B.; Jou, A.; Paredes, R.; Puig, J.; Llibre, J. M.; Santos, J. R.; Domingo, P.; Gutierrez, M.; Mateo, G.; Sambeat, M. A.; Laporte, J. M.; Falconer, K.; Thalme, A.; Sonnerborg, A.; Brannstrom, J.; Flamholc, L.; Scherrer, A.; Weber, R.; Cavassini, M.; Calmy, A.; Furrer, H.; Battegay, M.; Schmid, P.; Kuznetsova, A.; Mikhalik, J.; Sluzhynska, M.; Milinkovic, A.; Johnson, A. M.; Simons, E.; Edwards, S.; Phillips, A.; Johnson, M. A.; Mocroft, A.; Orkin, C.; Winston, A.; Clarke, A.; Leen, C.; Karpov, I.; Losso, M.; Lundgren, J.; Rockstroh, J.; Aho, I.; Rasmussen, L. D.; Svedhem, V.; Wandeler, G.; Pradier, C.; Chkhartishvili, N.; Matulionyte, R.; Oprea, C.; Kowalska, J. D.; Begovac, J.; Miro, J. M.; Guaraldi, G.; Paredes, R.; Wandeler, G.; Paredes, R.; Peters, L.; Kirk, O.; Peters, L.; Bojesen, A.; Raben, D.; Hansen, E. V.; Kristensen, D.; Larsen, J. F.; Fischer, A. H.; Mocroft, A.; Phillips, A.; Cozzi-Lepri, A.; Amele, S.; Pelchen-Matthews, A.; Roen, A.; Tusch, E.; Bannister, W.; Reekie, J.
abstract

Objectives: Although direct-acting antivirals (DAAs) can clear HCV in nearly all HIV/HCV-coinfected individuals, high rates of reinfection may hamper efforts to eliminate HCV in this population. We investigated reinfection after sustained virological response (SVR) in HIV/HCV-coinfected individuals in Europe. Methods: Factors associated with odds of reinfection by 2 years after SVR in EuroSIDA participants with one or more HCV-RNA test and 2 years follow-up were assessed using logistic regression. Results: Overall, 1022 individuals were included. The median age was 50 (interquartile range: 43–54 years), and most were male (78%), injection drug users (52%), and received interferon (IFN)-free DAAs (62%). By 24 months, 75 [7.3%, 95% confidence interval (CI): 5.7–8.9%] individuals were reinfected. Among individuals treated prior to 2014, 16.1% were reinfected compared with 4.2% and 8.3%, respectively, among those treated during or after 2014 with IFN-free and IFN-based therapy. After adjustment, individuals who had started treatment during or after 2014 with IFN-free or IFN-based therapy had significantly lower odds of reinfection (adjusted odds ratio = 0.21, 95% CI: 0.11–0.38; 0.43, 95% CI: 0.22–0.83) compared with those who had received therapy before 2014. There were no significant differences in odds of reinfection according to age, gender, European region, HIV transmission risk group or liver fibrosis. Conclusions: Among HIV/HCV-coinfected individuals in Europe, 7.3% were reinfected with HCV within 24 months of achieving SVR, with evidence suggesting that this is decreasing over time and with use of newer HCV regimens. Harm reduction to reduce reinfection and surveillance to detect early reinfection with an offer of treatment are essential to eliminate HCV.

2022 - HIV and syphilis: incidence rate of co-infection and syphilis re-infection in a cohort of newly diagnosed HIV patients [Articolo su rivista]
DI Tullio, Francesca; Mandel, Victor D; Cuomo, Gianluca; Coppini, Maurizio; Guaraldi, Giovanni; Mussini, Cristina; Pellacani, Giovanni; Borghi, Vanni
abstract

Syphilis represents a major public health concern disproportionately affecting HIV positive patients and in many cases both infections are newly diagnosed at the same time. To date, limited studies are available on syphilis incidence in patients with a new HIV diagnosis.

2022 - Hormone therapy in postmenopausal women living with HIV: a view towards prevention of multiple metabolic conditions and improvement of quality of life [Articolo su rivista]
Milic, J.; Guaraldi, G.
abstract

2022 - Imaging-based indices combining disease severity and time from disease onset to predict COVID-19 mortality: A cohort study [Articolo su rivista]
Besutti, Giulia; Djuric, Olivera; Ottone, Marta; Monelli, Filippo; Lazzari, Patrizia; Ascari, Francesco; Ligabue, Guido; Guaraldi, Giovanni; Pezzuto, Giuseppe; Bechtold, Petra; Massari, Marco; Lattuada, Ivana; Luppi, Francesco; Galli, Maria Giulia; Pattacini, Pierpaolo; Giorgi Rossi, Paolo
abstract

Background: COVID-19 prognostic factors include age, sex, comorbidities, laboratory and imaging findings, and time from symptom onset to seeking care. Purpose: The study aim was to evaluate indices combining disease severity measures and time from disease onset to predict mortality of COVID-19 patients admitted to the emergency department (ED). Materials and methods: All consecutive COVID-19 patients who underwent both computed tomography (CT) and chest X-ray (CXR) at ED presentation between 27/02/2020 and 13/03/2020 were included. CT visual score of disease extension and CXR Radiographic Assessment of Lung Edema (RALE) score were collected. The CT- and CXR-based scores, C-reactive protein (CRP), and oxygen saturation levels (sO2) were separately combined with time from symptom onset to ED presentation to obtain severity/time indices. Multivariable regression age- and sex-adjusted models without and with severity/time indices were compared. For CXR-RALE, the models were tested in a validation cohort. Results: Of the 308 included patients, 55 (17.9%) died. In multivariable logistic age- and sex-adjusted models for death at 30 days, severity/time indices showed good discrimination ability, higher for imaging than for laboratory measures (AUCCT = 0.92, AUCCXR = 0.90, AUCCRP = 0.88, AUCsO2 = 0.88). AUCCXR was lower in the validation cohort (0.79). The models including severity/time indices performed slightly better than models including measures of disease severity not combined with time and those including the Charlson Comorbidity Index, except for CRP-based models. Conclusion: Time from symptom onset to ED admission is a strong prognostic factor and provides added value to the interpretation of imaging and laboratory findings at ED presentation.

2022 - Intravenous methylprednisolone pulses in hospitalised patients with severe COVID-19 pneumonia, A double-blind, randomised, placebo-controlled trial [Articolo su rivista]
Salvarani, Carlo; Massari, Marco; Costantini, Massimo; Franco Merlo, Domenico; Lucia Mariani, Gabriella; Viale, Pierluigi; Nava, Stefano; Guaraldi, Giovanni; Dolci, Giovanni; Boni, Luca; Savoldi, Luisa; Bruzzi, Paolo; Turrà, Caterina; Catanoso, Mariagrazia; Maria Marata, Anna; Barbieri, Chiara; Valcavi, Annamaria; Franzoni, Francesca; Cavuto, Silvio; Mazzi, Giorgio; Corsini, Romina; Trapani, Fabio; Bartoloni, Alessandro; Barisione, Emanuela; Barbieri, Chiara; Jole Burastero, Giulia; Pan, Angelo; Inojosa, Walter; Scala, Raffaele; Burattini, Cecilia; Luppi, Fabrizio; Codeluppi, Mauro; Eldin Tarek, Kamal; Cenderello, Giovanni; Salio, Mario; Foti, Giuseppe; Dongilli, Roberto; Bajocchi, Gianluigi; Alberto Negri, Emanuele; Ciusa, Giacomo; Fornaro, Giacomo; Bassi, Ilaria; Zammarchi, Lorenzo; Aloè, Teresita; Facciolongo, Nicola
abstract

Rationale: Pulse glucocorticoid therapy is used in hyperinflammation related to coronavirus 2019 (COVID-19). We evaluated the efficacy and safety of pulse intravenous methylprednisolone in addition to standard treatment in COVID-19 pneumonia. Methods: In this multicenter, randomised, double-blind, placebo-controlled trial, 304 hospitalised patients with Covid-19 pneumonia were randomised to receive 1 g of methylprednisolone intravenously for 3 consecutive days or placebo in addition to standard dexamethasone. The primary outcome was the duration of the patient hospitalisation, calculated as the time interval between randomisation and hospital discharge without the need of supplementary oxygen. The key secondary outcomes were survival free from invasive ventilation with orotracheal intubation and overall survival. Results: Overall, 112 of 151 (75.4%) patients in the pulse methylprednisolone arm and 111 of 150 (75.2%) in the placebo arm were discharged from hospital without oxygen within 30 days from randomisation. Median time to discharge was similar in both groups [15 days (95% confidence interval (CI), 13.0 to 17.0) and 16 days (95%CI, 13.8 to 18.2); hazard ratio (HR), 0.92; 95% CI 0.71-1.20; p=0.528]. No significant differences between pulse methylprednisolone and placebo arms were observed in terms of admission to Intensive Care Unit with orotracheal intubation or death (20.0% versus 16.1%; HR, 1.26; 95%CI, 0.74-2.16; p=0.176), or overall mortality (10.0% versus 12.2%; HR, 0.83; 95%CI, 0.42-1.64; p=0.584). Serious adverse events occurred with similar frequency in the two groups. Conclusions: Methylprenisolone pulse therapy added to dexamethasone was not of benefit in patients with COVID-19 pneumonia. Message of the study: Pulse glucocorticoid therapy is used for severe and/or life threatening immuno-inflammatory diseases. The addition of pulse glucocorticoid therapy to the standard low dose of dexamethasone scheme was not of benefit in patients with COVID-19 pneumonia.

2022 - Machine learning algorithm to predict >5% Weight Gain in PWH switching to InSTI [Abstract in Atti di Convegno]
Guaraldi, Giovanni; Motta, Federico; Milić, Jovana; Barbieri, Sara; Gozzi, Licia; Aprile, Emanuele; Belli, Michela; Venuta, Maria; Cuomo, Gianluca; Carli, Federica; Dolci, Giovanni; Iadisernia, Vittorio; Burastero, Giulia; Mussini, Cristina; Mandreoli, Federica
abstract

2022 - Machine learning algorithm to predict >5% weight gain in PWH switching to INSTI [Poster]
Guaraldi, Giovanni; Motta, Federico; Milić, Jovana; Barbieri, Sara; Gozzi, Licia; Aprile, Emanuele; Belli, Michela; Venuta, Maria; Cuomo, Gianluca; Carli, Federica; Dolci, Giovanni; Iadisernia, Vittorio; Burastero, Giulia; Mussini, Cristina; Mandreoli, Federica
abstract

Background: Weight gain (WG) is a well-described phenomenon in PWH starting or switching ART. Machine learning (ML) methods is a tool of P4 medicine (Predictive, Preventive, Personalized & Participatory) and can generate models to identify patients at risk of WG. The objective was to develop an ML algorithm that predicts a 9-month WG≥5% in PLWH switching to InSTI with/without TAF. Methods: This was an observational study that comprised ART-experienced PWH attending Modena HIV metabolic clinic from 2004 to 2020. The patients' medical, HIV and ART data were partitioned in an 80/20 training/test set to generate predictive models. A ML model was used to leverage a hybrid approach where clinical expertise is applied along with data-driven analysis. The study outcome was the prediction at 9 months of weight change with a cut of 5%: at any patient visit (model 1) and in the subset of PWH switching to InSTI with/without TAF (model 2). 9-month prediction was chosen as being the minimum time occurring between any two given visits in the 95% of the cases. A robust implementation of linear regressor algorithms were able to predict weight gain/loss while tolerating missing data. Intelligible explanations were obtained through Shapley Additive exPlanations values (SHAP), which quantified the positive or negative impact of each variable included in each model on the predicted outcome. A measure of effectiveness (E-measure) was chosen as a performance metric, because unlike accuracy it can penalize errors, particularly underestimation ones. Results: A total of 2817 patients contributed to generate 10877 observations, which allowed construction of 2 predictive models based on 44-variables including anthropometric, HIV and laboratory biomarkers. At last observation median age was 51 years (IQR 11); 70% were male. Median CD4 nadir was 200 cells/μL (IQR 217), current CD4 was 659 cells/μL (IQR 372), 97% had undetectable VL and time since HIV diagnosis was 20 years (IQR 13). Median BMI was 23.4 (IQR 4.5) and 5.8% had obesity. The highest ranked variables used to train the models were weight at time of prediction and the ones depicted in the figure. Model 1 had accuracy of 84.4% and 83.9% E-measure; model 2 had accuracy of 84.4% and 86.4% E-measure. Conclusion: We developed a ML tool with a remarkable E-measure that may assist clinicians in decision-making and shift HIV care towards a P4 medicine. Immune-metabolic variables were more relevant than ART switching in the prediction of WG.

2022 - Machine learning algorithm to predict weight change in ART experienced PWH [Abstract in Atti di Convegno]
Motta, Federico; Milić, Jovana; Barbieri, Sara; Gozzi, Licia; Aprile, Emanuele; Belli, Michela; Venuta, Maria; Cuomo, Gianluca; Carli, Federica; Dolci, Giovanni; Iadisernia, Vittorio; Burastero, Giulia; Mussini, Cristina; Mandreoli, Federica; Guaraldi, Giovanni
abstract

2022 - Major revision version 11.0 of the European AIDS Clinical Society Guidelines 2021 [Articolo su rivista]
Ryom, Lene; De Miguel, Rosa; Cotter, Aoife Grace; Podlekareva, Daria; Beguelin, Charles; Waalewijn, Hylke; Arribas, Josè R; Mallon, Patrick W G; Marzolini, Catia; Kirk, Ole; Bamford, Alasdair; Rauch, Andri; Molina, Jean Michel; Kowalska, Justyna Dominika; Guaraldi, Giovanni; Winston, Alan; Boesecke, Christoph; Cinque, Paola; Welch, Steven; Collins, Simon; Behrens, Georg M N
abstract

Background The European AIDS Clinical Society (EACS) Guidelines were revised in 2021 for the 17th time with updates on all aspects of HIV care. Key points of the Guidelines update Version 11.0 of the Guidelines recommend six first-line treatment options for antiretroviral treatment (ART)-naive adults: tenofovir-based backbone plus an unboosted integrase inhibitor or plus doravirine; abacavir/lamivudine plus dolutegravir; or dual therapy with lamivudine or emtricitabine plus dolutegravir. Recommendations on preferred and alternative first-line combinations from birth to adolescence were included in the new paediatric section made with Penta. Long-acting cabotegravir plus rilpivirine was included as a switch option and, along with fostemsavir, was added to all drug-drug interaction (DDI) tables. Four new DDI tables for anti-tuberculosis drugs, anxiolytics, hormone replacement therapy and COVID-19 therapies were introduced, as well as guidance on screening and management of anxiety disorders, transgender health, sexual health for women and menopause. The sections on frailty, obesity and cancer were expanded, and recommendations for the management of people with diabetes and cardiovascular disease risk were revised extensively. Treatment of recently acquired hepatitis C is recommended with ongoing risk behaviour to reduce transmission. Bulevirtide was included as a treatment option for the hepatitis Delta virus. Drug-resistant tuberculosis guidance was adjusted in accordance with the 2020 World Health Organization recommendations. Finally, there is new guidance on COVID-19 management with a focus on continuance of HIV care. Conclusions In 2021, the EACS Guidelines were updated extensively and broadened to include new sections. The recommendations are available as a free app, in interactive web format and as an online pdf.

2022 - Metabolic reprograming shapes neutrophil functions in severe COVID-19 [Articolo su rivista]
Borella, Rebecca; De Biasi, Sara; Paolini, Annamaria; Boraldi, Federica; Tartaro, Domenico Lo; Mattioli, Marco; Fidanza, Lucia; Neroni, Anita; Caro-Maldonado, Alfredo; Meschiari, Marianna; Franceschini, Erica; Quaglino, Daniela; Guaraldi, Giovanni; Bertoldi, Carlo; Sita, Marco; Busani, Stefano; Girardis, Massimo; Mussini, Cristina; Cossarizza, Andrea; Gibellini, Lara
abstract

: To better understand the mechanisms at the basis of neutrophil functions during SARS-CoV-2 we studied patients with severe COVID-19 pneumonia. They had high blood proportion of degranulated neutrophils and elevated plasma levels of myeloperoxidase (MPO), elastase and MPO-DNA complexes, which are typical markers of neutrophil extracellular traps (NET). Their neutrophils display dysfunctional mitochondria, defective oxidative burst, increased glycolysis, glycogen accumulation in the cytoplasm, and increase glycogenolysis. Hypoxia-inducible factor 1α (ΗΙF-1α) is stabilized in such cells, and it controls the level of glycogen phosphorylase L (PYGL), a key enzyme in glycogenolysis. Inhibiting PYGL abolishes the ability of neutrophils to produce NET. Patients displayed significant increases of plasma levels of molecules involved in the regulation of neutrophils' function, including CCL2, CXCL10, CCL20, IL-18, IL-3, IL-6, G-CSF, GM-CSF, IFN-γ. Our data suggest that metabolic remodelling is vital for the formation of NET and for boosting neutrophil inflammatory response, thus suggesting that modulating ΗΙF-1α or PYGL could represent a novel approach for innovative therapies. This article is protected by copyright. All rights reserved.

2022 - Metabolic-Associated Fatty Liver Disease Is Highly Prevalent in the Postacute COVID Syndrome. [Articolo su rivista]
Milic, J; Barbieri, S; Gozzi, L; Brigo, A; Beghe', B; Verduri, A; Bacca, E; Iadisernia, V; Cuomo, G; Dolci, G; Yaacoub, D; Aprile, E; Belli, M; Venuta, M; Meschiari, M; Sebastiani, G; Clini, E; Mussini, C; Lonardo, A; Guaraldi, G; Raggi, P.
abstract

Background: A proposal has recently been advanced to change the traditional definition of nonalcoholic fatty liver disease to metabolic-associated fatty liver disease (MAFLD), to reflect the cluster of metabolic abnormalities that may be more closely associated with cardiovascular risk. Long coronavirus disease 2019 (COVID-19) is a smoldering inflammatory condition, characterized by several symptom clusters. This study aims to determine the prevalence of MAFLD in patients with postacute COVID syndrome (PACS) and its association with other PACS-cluster phenotypes. Methods: We included 235 patients observed at a single university outpatient clinic. The diagnosis of PACS was based on ≥1 cluster of symptoms: respiratory, neurocognitive, musculoskeletal, psychological, sensory, and dermatological. The outcome was prevalence of MAFLD detected by transient elastography during the first postdischarge follow-up outpatient visit. The prevalence of MAFLD at the time of hospital admission was calculated retrospectively using the hepatic steatosis index. Results: Of 235 patients, 162 (69%) were men (median age 61). The prevalence of MAFLD was 55.3% at follow-up and 37.3% on admission (P < .001). Insulin resistance (odds ratio [OR] = 1.5; 95% confidence interval [CI], 1.14-1.96), body mass index (OR = 1.14; 95% CI, 1.04-1.24), and the metabolic syndrome (OR = 2.54; 95% CI, 1.13-5.68) were independent predictors of MAFLD. The number of PACS clusters was inversely associated with MAFLD (OR = 0.86; 95% CI, .76-0.97). Thirty-one patients (13.2%) had MAFLD with no other associated PACS clusters. All correlations between MAFLD and other PACS clusters were weak. Conclusions: Metabolic-associated fatty liver disease was highly prevalent after hospital discharge and may represent a specific PACS-cluster phenotype, with potential long-term metabolic and cardiovascular health implications.

2022 - Minimal prevalence of HPV vaccination and common occurrence of high-risk HPV types in pregnant women with HIV: data from a national study in Italy [Articolo su rivista]
Floridia, M.; Masuelli, G.; Tassis, B.; Savasi, V. M.; Sansone, M.; Spinillo, A.; Franceschetti, L.; Guaraldi, G.; Pinnetti, C.; Dalzero, S.; Meloni, A.; Vimercati, A.; Simonazzi, G.; Tamburrini, E.; Ravizza, M.
abstract

Among 733 pregnant women with HIV followed between 2013 and 2021, only 8 (1.1%) had prior HPV vaccination. One had low-grade squamous intraepithelial lesions [LSIL], and none had HPV type information. Among the 725 non-vaccinated women, 578 (79.7%) had information on cervical cytology. Rate of cytologic abnormalities in this group was 20.6% (0.2% atypical glandular cells of undetermined significance [AGC], 1.7% atypical squamous cells of undetermined significance [ASC-US], 11.1% LSIL, and 7.6% high-grade squamous intraepithelial lesions [HSIL]). Among 56 women with HPV type information, 75.0% carried high risk types, with similar occurrence in women with and without cytologic abnormalities, 30.4% had multiple high-risk types, and 75.9% carried at least one of the types included in the currently recommended 9-valent vaccine.

2022 - Modifications of Chest CT Body Composition Parameters at Three and Six Months after Severe COVID-19 Pneumonia: A Retrospective Cohort Study [Articolo su rivista]
Besutti, Giulia; Pellegrini, Massimo; Ottone, Marta; Bonelli, Efrem; Monelli, Filippo; Farì, Roberto; Milic, Jovana; Dolci, Giovanni; Fasano, Tommaso; Canovi, Simone; Costi, Stefania; Fugazzaro, Stefania; Massari, Marco; Ligabue, Guido; Croci, Stefania; Salvarani, Carlo; Pattacini, Pierpaolo; Guaraldi, Giovanni; Giorgi Rossi, Paolo
abstract

We aimed to describe body composition changes up to 6-7 months after severe COVID-19 and to evaluate their association with COVID-19 inflammatory burden, described by the integral of the C-reactive protein (CRP) curve. The pectoral muscle area (PMA) and density (PMD), liver-to-spleen (L/S) ratio, and total, visceral, and intermuscular adipose tissue areas (TAT, VAT, and IMAT) were measured at baseline (T0), 2-3 months (T1), and 6-7 months (T2) follow-up CT scans of severe COVID-19 pneumonia survivors. Among the 208 included patients (mean age 65.6 ± 11 years, 31.3% females), decreases in PMA [mean (95%CI) -1.11 (-1.72; -0.51) cm2] and in body fat areas were observed [-3.13 (-10.79; +4.52) cm2 for TAT], larger from T0 to T1 than from T1 to T2. PMD increased only from T1 to T2 [+3.07 (+2.08; +4.06) HU]. Mean decreases were more evident for VAT [-3.55 (-4.94; -2.17) cm2] and steatosis [L/S ratio increase +0.17 (+0.13; +0.20)] than for TAT. In multivariable models adjusted by age, sex, and baseline TAT, increasing the CRP interval was associated with greater PMA reductions, smaller PMD increases, and greater VAT and steatosis decreases, but it was not associated with TAT decreases. In conclusion, muscle loss and fat loss (more apparent in visceral compartments) continue until 6-7 months after COVID-19. The inflammatory burden is associated with skeletal muscle loss and visceral/liver fat loss.

2022 - Molecular and cellular immune features of aged patients with severe COVID-19 pneumonia [Articolo su rivista]
Lo Tartaro, D.; Neroni, A.; Paolini, A.; Borella, R.; Mattioli, M.; Fidanza, L.; Quong, A.; Petes, C.; Awong, G.; Douglas, S.; Lin, D.; Nieto, J.; Gozzi, L.; Franceschini, E.; Busani, S.; Nasi, M.; Mattioli, A. V.; Trenti, T.; Meschiari, M.; Guaraldi, G.; Girardis, M.; Mussini, C.; Gibellini, L.; Cossarizza, A.; De Biasi, S.
abstract

Aging is a major risk factor for developing severe COVID-19, but few detailed data are available concerning immunological changes after infection in aged individuals. Here we describe main immune characteristics in 31 patients with severe SARS-CoV-2 infection who were >70 years old, compared to 33 subjects <60 years of age. Differences in plasma levels of 62 cytokines, landscape of peripheral blood mononuclear cells, T cell repertoire, transcriptome of central memory CD4+ T cells, specific antibodies are reported along with features of lung macrophages. Elderly subjects have higher levels of pro-inflammatory cytokines, more circulating plasmablasts, reduced plasmatic level of anti-S and anti-RBD IgG3 antibodies, lower proportions of central memory CD4+ T cells, more immature monocytes and CD56+ pro-inflammatory monocytes, lower percentages of circulating follicular helper T cells (cTfh), antigen-specific cTfh cells with a less activated transcriptomic profile, lung resident activated macrophages that promote collagen deposition and fibrosis. Our study underlines the importance of inflammation in the response to SARS-CoV-2 and suggests that inflammaging, coupled with the inability to mount a proper anti-viral response, could exacerbate disease severity and the worst clinical outcome in old patients.

2022 - Monkeypox vaccination—an opportunity for HIV prevention [Articolo su rivista]
Mussini, Cristina; Guaraldi, Giovanni; Orkin, Chloe
abstract

2022 - Non-alcoholic to metabolic associated fatty liver disease: Cardiovascular implications of a change in terminology in patients living with HIV [Abstract in Atti di Convegno]
Raggi, Paolo; Milić, Jovana; Renzetti, Stefano; Motta, Federico; Gozzi, Licia; Cervo, Adriana; Burastero, Giulia; Iadisernia, Vittorio; Franceschi, Giacomo; Faltoni, Matteo; Mussini, Cristina; Sebastiani, Giada; Calza, Stefano; Guaraldi, Giovanni
abstract

Background and Aims: It has recently been suggested that the definition of non-alcoholic fatty liver disease (NAFLD) be changed to Metabolic Associated FLD (MAFLD) to better reflect the complex metabolic aspects of this syndrome. We compared the ability of MAFLD and NAFLD to correctly identify high CV risk patients, sub-clinical atherosclerosis or a history of prior CV events (CVEs) in patients living with HIV (PWH). Methods: Single center, cross-sectional study of PWH on stable anti-retrovirals. NAFLD was diagnosed by transient liver elastography; published criteria were used to diagnose MAFLD (JHepatol.2020;73(1):202-209). Four mutually exclusive groups were considered: low (<7.5%) vs high (>7.5%) ASCVD risk, subclinical CVD (carotid IMT ≥1 mm and/or coronary calcium score >100), and prior CVEs. The association of NAFLD and MAFLD with the CVD risk groups was explored via a multinominal model adjusted for age, sex, liver fibrosis, HIV duration, nadir CD4 and current CD4 cell count. Results: We included 1249 PWH (mean age 55 years, 74% men, median HIV duration 24 years). Prevalence of overweight/obesity and diabetes was 40% and 18%. Prevalence of NAFLD and MAFLD and overlapping groups are shown in Fig 1A. Fig 1B shows distribution of NAFLD/MAFLD in the 4 patient categories (p-for-trend <0.001). Both MAFLD and NAFLD were significantly associated with an increased risk of CVD compared to the reference level (ASCVD<7.5%) (all p-values <0.004; Fig 2). Conclusions: NAFLD and MAFLD perform equally in detecting CVD or its risk. The proposed change in terminology may not help to identify PWH requiring enhanced surveillance and preventative interventions for cardiovascular disease.

2022 - Non–alcoholic to metabolic associated fatty liver disease: cardiovascular implications of a change in terminology in patients living with HIV [Abstract in Atti di Convegno]
Milić, Jovana; Renzetti, Stefano; Motta, Federico; Gozzi, Licia; Cervo, Adriana; Burastero, Giulia; Iadisernia, Vittorio; Franceschi, Giacomo; Faltoni, Matteo; Volpi, Sara; Mazzocchi, Alice; Mussini, Cristina; Sebastiani, Giada; Calza, Stefano; Raggi, Paolo; Guaraldi, Giovanni
abstract

2022 - Patients Recovering from Severe COVID-19 Develop a Polyfunctional Antigen-Specific CD4+ T Cell Response [Articolo su rivista]
Paolini, A.; Borella, R.; Neroni, A.; Lo Tartaro, D.; Mattioli, M.; Fidanza, L.; Di Nella, A.; Santacroce, E.; Gozzi, L.; Busani, S.; Trenti, T.; Meschiari, M.; Guaraldi, G.; Girardis, M.; Mussini, C.; Gibellini, L.; De Biasi, S.; Cossarizza, A.
abstract

Specific T cells are crucial to control SARS-CoV-2 infection, avoid reinfection and confer protection after vaccination. We have studied patients with severe or moderate COVID-19 pneumonia, compared to patients who recovered from a severe or moderate infection that had occurred about 4 months before the analyses. In all these subjects, we assessed the polyfunctionality of virus-specific CD4+ and CD8+ T cells by quantifying cytokine production after in vitro stimulation with different SARS-CoV-2 peptide pools covering different proteins (M, N and S). In particular, we quantified the percentage of CD4+ and CD8+ T cells simultaneously producing interferon-γ, tumor necrosis factor, interleukin (IL)-2, IL-17, granzyme B, and expressing CD107a. Recovered patients who experienced a severe disease display high proportions of antigen-specific CD4+ T cells producing Th1 and Th17 cytokines and are characterized by polyfunctional SARS-CoV-2-specific CD4+ T cells. A similar profile was found in patients experiencing a moderate form of COVID-19 pneumonia. No main differences in polyfunctionality were observed among the CD8+ T cell compartments, even if the proportion of responding cells was higher during the infection. The identification of those functional cell subsets that might influence protection can thus help in better understanding the complexity of immune response to SARS-CoV-2.

2022 - Plasma Cytokine Atlas Reveals the Importance of TH2 Polarization and Interferons in Predicting COVID-19 Severity and Survival [Articolo su rivista]
Gibellini, L.; De Biasi, S.; Meschiari, M.; Gozzi, L.; Paolini, A.; Borella, R.; Mattioli, M.; Lo Tartaro, D.; Fidanza, L.; Neroni, A.; Busani, S.; Girardis, M.; Guaraldi, G.; Mussini, C.; Cozzi-Lepri, A.; Cossarizza, A.
abstract

Although it is now widely accepted that host inflammatory response contributes to COVID-19 immunopathogenesis, the pathways and mechanisms driving disease severity and clinical outcome remain poorly understood. In the effort to identify key soluble mediators that characterize life-threatening COVID-19, we quantified 62 cytokines, chemokines and other factors involved in inflammation and immunity in plasma samples, collected at hospital admission, from 80 hospitalized patients with severe COVID-19 disease who were stratified on the basis of clinical outcome (mechanical ventilation or death by day 28). Our data confirm that age, as well as neutrophilia, lymphocytopenia, procalcitonin, D-dimer and lactate dehydrogenase are strongly associated with the risk of fatal COVID-19. In addition, we found that cytokines related to TH2 regulations (IL-4, IL-13, IL-33), cell metabolism (lep, lep-R) and interferons (IFNα, IFNβ, IFNγ) were also predictive of life-threatening COVID-19.

2022 - Primary, secondary and compensated male biochemical hypogonadism in people living with HIV (PLWH): relevance of sex hormone-binding globulin (SHBG) measurement and comparison between liquid chromatography-tandem mass spectrometry (LC-MS/MS) and chemiluminescent immunoassay for sex steroids assay [Articolo su rivista]
De Vincentis, Sara; Decaroli, Maria Chiara; Fanelli, Flaminia; Diazzi, Chiara; Mezzullo, Marco; Tartaro, Giulia; Tagliavini, Simonetta; De Santis, Maria Cristina; Roli, Laura; Milic, Jovana; Trenti, Tommaso; Pagotto, Uberto; Guaraldi, Giovanni; Rochira, Vincenzo
abstract

Background: Data about classification of hypogonadism and estrogen deficiency in male people living with HIV (PLWH) are scanty. Aim: To investigate the prevalence and characterization of biochemical hypogonadism and relative estrogen deficiency in male PLWH aged < 50 comparing liquid chromatography-tandem mass spectrometry (LC-MS/MS) with chemiluminescent immunoassay (CI), and combining gonadotropin, sex hormone-binding globulin (SHBG) and serum estradiol (E2) measurements. Methods: Prospective, cross-sectional, observational study. Serum total testosterone (TT), E2, gonadotropins, SHBG were measured by CI. TT and E2 were also assessed by LC-MS/MS. Free testosterone (cFT) was calculated by Vermeulen equation. Results: A total of 316 PLWH (45.3 ± 5.3 years) were enrolled. TT and cFT by LC-MS/MS were lower compared to CI (p < 0.0001). The prevalence of biochemical hypogonadism was higher with LC-MS/MS than CI, both for TT (5.1% vs 3.2%, p < 0.0001) or cFT (9.5% vs 7%, p < 0.0001). The prevalence of hypogonadism (overt + compensated) was 17.1% for cFT using LC-MS/MS. Secondary form of hypogonadism was more prevalent than primary. The prevalence of relative estrogen deficiency was of 30.0% among hypogonadal patients and 15.5% among eugonadal. Conclusions: The prevalence of male hypogonadism results underestimated by CI compared to LC-MS/MS in PLWH, both for TT and cFT. SHBG and gonadotropins are essential for detecting T deficiency.

2022 - Reactogenicity of COVID-19 vaccine in hemodialysis patients: a single-center retrospective study [Articolo su rivista]
Alfano, Gaetano; Morisi, Niccolò; Fontana, Francesco; Scarmignan, Roberta; Tonelli, Laura; Ferri, Camilla; Montani, Martina; Melluso, Andrea; Giovanella, Silvia; Ligabue, Giulia; Mori, Giacomo; Franceschini, Erica; Guaraldi, Giovanni; Cappelli, Gianni; Magistroni, Riccardo; Donati, Gabriele
abstract

: Introduction: Some hemodialysis patients are reluctant to undergo COVID-19 vaccination for the fear of developing adverse events (AEs). The aim of this study was to verify the safety of the mRNA-1273 vaccine in hemodialysis patients. Methods: We conducted a retrospective analysis of in-center hemodialysis patients who underwent mRNA-1273 vaccine from March 1st to April 30th, 2021. All AEs occurring after the first and the second doses were collected and classified as local or systemic. Results: Overall, 126 patients on chronic maintenance dialysis without a prior COVID-19 diagnosis were vaccinated with two doses of mRNA-1273 vaccine. Mean age was 68 (IQR, 54,7-76) years and 53.6% of patients were aged ≥65 years. During the observational period of 68 (IQR, 66-70) days, AEs occurred in 57.9% and 61.9% of patients after the first dose and second dose, respectively. The most common AEs were: injection-site pain (61.9%), erythema (4.8%), itching (4.8%), swelling (16.7%), axillary swelling/tenderness (2.4%), fever (17.5%) headache (7.9%), fatigue (23.8%), myalgia (17.5%), arthralgia (12.7%), dyspnoea (2.4%), nausea/vomiting (7.1%), diarrhoea (5.6%), shivers (4%) and vertigo (1.6%). The rates of local AEs were similar after the first and second doses (P=0.8), whereas systemic AEs occurred more frequently after the second dose (P=0.001). Fever (P=0.03), fatigue (P=0.02) and nausea/vomiting (P=0.03) were significantly more frequent after the second dose of the vaccine. There were no age-related differences in the rate of AEs. Overall, vaccine-related AEs in hemodialysis patients seem to be lower than in the general population. Conclusion: The RNA-1273 vaccine was associated with the development of transient AEs after the first and second doses in patients on chronic maintenance hemodialysis. They were mostly local, whereas systemic AEs were more prevalent after the second dose. Overall, all AEs lasted for a few days, without any apparent sequelae.

2022 - Relationship between weight gain and insulin resistance in people living with HIV switching to INSTI-based regimens [Articolo su rivista]
Milic, Jovana; Renzetti, Stefano; Ferrari, Davide; Barbieri, Sara; Menozzi, Marianna; Carli, Federica; Dolci, Giovanni; Ciusa, Giacomo; Mussini, Cristina; Calza, Stefano; Guaraldi, Giovanni
abstract

Objective: The primary objective was to explore weight and BMI changes in people with HIV (PWH) undergoing integrase strand transfer inhibitors (INSTI)-based regimens (vs. non-INSTI) in a large cohort and in the subsets of individuals without diabetes and insulin resistance (IR) at the time of switch to INSTI. The secondary objective was to identify risk factors for IR and cut-off of weight or BMI increase associated with IR in PWH switching to INSTI. Design: A longitudinal matched-cohort study including PWH attending Modena HIV Metabolic Clinic, Italy. Methods: PWH were divided into two groups: non-INSTI and INSTI-switch. The effect of switching to INSTI on weight and BMI change was tested through a linear mixed model. A mediation analysis explored the mediation effect of weight and BMI change in the association between the switch to INSTI and IR. Results: We analyzed 2437 PWH (1025 INSTI-switch, 1412 non-INSTI), in 54 826 weight assessments. Trends for weight increase were significantly higher in early-INSTI-switch (vs. early-non-INSTI), but no difference was observed in the late period after the switch. In the subset of 634 PWH without IR, switching to INSTI (vs. non-INSTI) was associated with a lower risk of IR (hazard ratio = 0.70, 95% confidence interval: 0.51, 0.98). A weight increase by 1% reduced the total protective effect of INSTI by 21.1% over 1 year of follow-up, which identifies a 5% weight increase as a clinically meaningful weight gain definition. Conclusion: A cut-off of 5% weight gain from the time of INSTI-switch is associated with IR, which may be a clinically meaningful endpoint to could be used in clinical and research settings.

2022 - Resilience and Frailty in People Living With HIV During the COVID Era: Two Complementary Constructs Associated With Health-Related Quality of Life [Articolo su rivista]
Guaraldi, Giovanni; Milic, Jovana; Barbieri, Sara; Marchiò, Tommaso; Caselgrandi, Agnese; Volpi, Sara; Aprile, Emanuele; Belli, Michela; Venuta, Maria; Mussini, Cristina
abstract

Background: Resilience is defined as an individual's positive adaptation to stressors. The COVID-19 pandemic represents a generalized stressor which may affect differently people living with HIV (PLWH). The objective of this study was to characterize resilience in PLWH with particular regarding the identification of frailty-resilience phenotypes, which may differently affect health-related quality of life (HR-QoL). Methods: This was an observational study of PLWH attending Modena HIV Metabolic Clinic. Frailty was assessed in 2019, before the onset of the COVID-19 pandemic by using 37-Item frailty index ranging from 0 to 1. The frailty index score was categorized as fit (<0.25) or frail (>0.25). In January 2021, PLWH were offered to complete a set of electronic questionnaires including the CD-RISC-25 for resilience and EQ-5D5L and SF-36 for HR-QoL. Resilience was defined as CD-RISC-25 score >75.7 (ranging from 0 to 100). Results: Of 800 PLWH reached by mail, 575 (72%) completed the questionnaires. The median age and HIV duration were 54.5 and 24.3 years, respectively. Impaired resilience was associated with loneliness [odds ratio (OR = 2.39; 1.20 to 4.76, P < 0.001)]. Predictors for EQ-5D5L <89.7% were the phenotypes "frail/nonresilient" [OR = 5.21, 95% confidence interval (CI): 2.62 to 10.33] and "fit/nonresilient" (OR = 5.48, 95% CI: 2.8 to 10.74). Predictors for SF-36 <64.40 were the phenotypes "frail/nonresilient" (OR = 7.43, 95% CI: 2.57 to 21.22) and "fit/nonresilient" (OR = 6.27, 95% CI: 2.17 to 18.16). Both models were corrected for age, sex, HIV duration, and nadir CD4. Conclusions: Resilience characterizes the well-being of PLWH during the COVID-19 crisis. This construct is complementary to frailty in the identification of clinical phenotypes with different impacts on HR-QoL.

2022 - Response to: weight gain stopping/switch rules for antiretroviral clinical trials [Articolo su rivista]
Taramasso, Lucia; Di Biagio, Antonio; Guaraldi, Giovanni
abstract

2022 - Switch back from TAF to TDF or rather switch forward from metabolic toxicities of drugs to metabolic health of people living with HIV [Articolo su rivista]
Stapleton, Jack T; Bedimo, Roger J; Guaraldi, Giovanni
abstract

2022 - The interplay of post-acute COVID-19 syndrome and aging: a biological, clinical and public health approach [Articolo su rivista]
Guaraldi, Giovanni; Milic, Jovana; Cesari, Matteo; Leibovici, Leonard; Mandreoli, Federica; Missier, Paolo; Rozzini, Renzo; Cattelan, Anna Maria; Motta, Federico; Mussini, Cristina; Cossarizza, Andrea
abstract

The post-acute COVID-19 syndrome (PACS) is characterized by the persistence of fluctuating symptoms over three months from the onset of the possible or confirmed COVID-19 acute phase. Current data suggests that at least 10% of people with previously documented infection may develop PACS, and up to 50-80% of prevalence is reported among survivors after hospital discharge. This viewpoint will discuss various aspects of PACS, particularly in older adults, with a specific hypothesis to describe PACS as the expression of a modified aging trajectory induced by SARS CoV-2. This hypothesis will be argued from biological, clinical and public health view, addressing three main questions: (i) does SARS-CoV-2-induced alterations in aging trajectories play a role in PACS?; (ii) do people with PACS face immuno-metabolic derangements that lead to increased susceptibility to age-related diseases?; (iii) is it possible to restore the healthy aging trajectory followed by the individual before pre-COVID?. A particular focus will be given to the well-being of people with PACS that could be assessed by the intrinsic capacity model and support the definition of the healthy aging trajectory.

2022 - The pathway of NAFLD vs MAFLD toward significant fibrosis [Abstract in Atti di Convegno]
Milić, Jovana; Renzetti, Stefano; Motta, Federico; Gozzi, Licia; Besutti, Giulia; Burastero, Giulia; Iadisernia, Vittorio; Dessilani, Andrea; Del Monte, Martina; Faltoni, Matteo; Volpi, Sara; Lebouche, Bertrand; Al Hinai, Shaima; Deschenes, Marc; Calza, Stefano; Raggi, Paolo; Mancini, Giuseppe; Mussini, Cristina; Sebastiani, Giada; Guaraldi, Giovanni
abstract

2022 - The pathway of NAFLD vs MAFLD toward significant fibrosis [Abstract in Atti di Convegno]
Milić, Jovana; Renzetti, Stefano; Motta, Federico; Gozzi, Licia; Besutti, Giulia; Burastero, Giulia; Iadisernia, Vittorio; Lebouché, Bertrand; Al Hinai, Shaima; Deschenes, Marc; Calza, Stefano; Mussini, Cristina; Sebastiani, Giada; Guaraldi, Giovanni
abstract

2022 - The Relationship between Visceral Adiposity and Nonalcoholic Fatty Liver Disease Diagnosed by Controlled Attenuation Parameter in People with HIV: A Pilot Study [Articolo su rivista]
Sebastiani, Giada; Paisible, Nathalie; Costiniuk, Cecilia; Cox, Joseph; Kablawi, Dana; Klein, Marina B; Kronfli, Nadine; Routy, Jean-Pierre; Falutz, Julian; Lebouché, Bertrand; Guaraldi, Giovanni
abstract

Background: Fat alterations are frequent in people with HIV (PWH) and predict worse cardiometabolic outcomes. Visceral adipose tissue (VAT) is associated with ectopic fat accumulation in the liver. We aimed to investigate nonalcoholic fatty liver disease (NAFLD) diagnosed by controlled attenuation parameter (CAP) as a potential marker of visceral adiposity in PWH. Methods: We conducted a prospective pilot study of HIV mono-infected patients undergoing metabolic characterization and paired CAP measured by transient elastography with dual-energy X-ray absorptiometry (DEXA) scan. NAFLD was defined as CAP >= 285 dB/m, in absence of alcohol abuse. Excess visceral adiposity was defined as VAT > 1.32 Kg. Pairwise correlation, area under the curve (AUC) and logistic regression analysis were employed to study the association between VAT and CAP. Results: Thirty patients were included, of whom 50% had NAFLD. CAP was correlated with VAT (r = 0.650, p < 0.001) measured by DEXA scan. After adjusting for duration of HIV infection, body mass index and waist circumference, CAP remained the only independent predictor of excess VAT (adjusted odds ratio 1.05, 95% confidence interval [CI] 1.01-1.10). The AUC analysis determined CAP had excellent performance to diagnose excess VAT (AUC 0.92, 95% CI 0.81-1.00), higher than BMI and waist circumference. The optimized CAP cut-off to diagnose excess VAT was 266 dB/m, with a sensitivity of 88.3% and a specificity of 84.6%. Conclusions: NAFLD diagnosed by CAP is associated with VAT in PWH independently of anthropometric measures of obesity. CAP may be a potential diagnostic marker of visceral adiposity in the practice of HIV medicine.

2022 - Two-Tier Care Pathways for Liver Fibrosis Associated to Non-Alcoholic Fatty Liver Disease in HIV Mono-Infected Patients [Articolo su rivista]
Sebastiani, Giada; Milic, Jovana; Cervo, Adriana; Saeed, Sahar; Krahn, Thomas; Kablawi, Dana; Al Hinai, Al Shaima; Lebouché, Bertrand; Wong, Philip; Deschenes, Marc; Gioè, Claudia; Cascio, Antonio; Mazzola, Giovanni; Guaraldi, Giovanni
abstract

2022 - Weekly Rapid Antigen Test Screening for COVID-19 in Patients on Hemodialysis [Articolo su rivista]
Alfano, Gaetano; Scarmignan, Roberta; Amurri, Alessio; Fontana, Francesco; Giovanella, Silvia; Ligabue, Giulia; Gennari, William; Pecorari, Monica; Sarti, Mario; Guaraldi, Giovanni; Cappelli, Gianni; Gregorini, Mariacristina; Magistroni, Riccardo; Donati, Gabriele
abstract

COVID-19 is a concerning issue among in-center hemodialysis (HD) patients. To prevent COVID-19 diffusion in our HD facility, weekly rapid nasal antigen test screening was performed for all asymptomatic patients on chronic HD. This study aimed to assess the performance of weekly rapid antigen test in detecting SARS-CoV-2 infection among asymptomatic patients receiving HD.

2022 - Which criteria should we use to end isolation in hemodialysis patients with COVID-19? [Articolo su rivista]
Alfano, G.; Fontana, F.; Ferrari, A.; Morisi, N.; Gregorini, M.; Cappelli, G.; Magistroni, R.; Guaraldi, G.; Donati, G.
abstract

Safe and timely discontinuation of quarantine of in-center hemodialysis (HD) patients with a previous severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is a challenging issue for the nephrological community because current guidelines for ending isolation do not mention dialysis patients. To prevent potentially fatal outbreaks of coronavirus disease 2019 (COVID-19), a cautionary approach has been adopted by most dialysis units. The criteria for ending the isolation in the HD population generally coincide with those recommended for immunocompromised people. Thus, a test-based strategy relying on two consecutive negative reverse transcriptase-polymerase chain reaction (RT-PCR) nasopharyngeal swabs has been adopted to terminate quarantine. This strategy has the disadvantage of prolonging isolation as RT-PCR positivity does not equate to SARS-CoV-2 infectivity. Consequentially, prolonged positivity of SARS-CoV-2 results in excessive workload for the HD staff who must face an increasing number of COVID-19 patients requiring isolation. This condition leads also to serious implications for the patients and their households including work productivity loss, postponement of health-care appointments and an increased risk of COVID-19 reinfection. To counteract this problem, other diagnostic tests should be used to provide the best care to HD patients. Recent results seem to encourage the use of RT-PCR cycle threshold (Ct) values and rapid antigen tests given their better correlation with cell culture for SARS-CoV-2 than RT-PCR testing. Here, we provide an overview of the current scientific evidence on the tests used to verify the infectiousness of the virus in order to stimulate the nephrological community to adopt a streamlined and pragmatic procedure to end isolation in COVID-19 patients on HD.

2021 - Adherence to Lipid-Lowering Medication in People Living with HIV: An Outpatient Clinic Drug Direct Distribution Experience [Articolo su rivista]
Cuomo, Gianluca; Raimondi, Alessandro; Rivasi, Marianna; Guaraldi, Giovanni; Borghi, Vanni; Mussini, Cristina
abstract

Adherence to lipid-lowering drugs could be challenging in our patients as it is in the general population, which is described as low as 25%. Our aim was to evaluate adherence to statins and to investigate clinical event impact on it.

2021 - AKI in hospitalized patients with COVID-19: a single-center experience [Articolo su rivista]
Alfano, Gaetano; Giovanella, Silvia; Fontana, Francesco; Milic, Jovana; Ligabue, Giulia; Morisi, Niccolò; Giaroni, Francesco; Mori, Giacomo; Magistroni, Riccardo; Franceschini, Erica; Bedini, Andrea; Cuomo, Giacomo; Digaetano, Margherita; Meschiari, Marianna; Mussini, Cristina; Cappelli, Gianni; Guaraldi, Giovanni
abstract

2021 - Alzheimer Dementia in People Living With HIV [Articolo su rivista]
Calcagno, Andrea; Celani, Luigi; Trunfio, Mattia; Orofino, Giancarlo; Imperiale, Daniele; Atzori, Cristiana; Arena, Vincenzo; D'Ettorre, Gabriella; Guaraldi, Giovanni; Gisslen, Magnus; Di Perri, Giovanni
abstract

ObjectiveGiven the aging of people living with HIV (PLWH) and the high prevalence of HIV-associated neurocognitive disorders, we aimed at describing the clinical, instrumental, and CSF features of PLWH diagnosed with Alzheimer dementia (AD).MethodsThe databases of 3 large Italian outpatient clinics taking care of more than 9,000 PLWH were searched for the diagnosis of AD. After obtaining patients' or their next of kin's consent for publication, anonymous data were collected in an excel spreadsheet and described. Routinely collected CSF biomarkers and radiologic imaging results were recorded whether available.ResultsFour patients were included in this case series who were diagnosed with AD aged between 60 and 74 years. All participants were on highly active antiretroviral therapy and showed nondetectable serum HIV RNA. Memory impairment was the most prominent cognitive feature. The diagnosis was obtained considering the exclusion of other potential causes, MRI and fluorodeoxyglucose-PET features, and, in (in 2/4), CSF AD biomarkers levels. In 1 patient, longitudinal CSF tau/p-tau increased, and beta-amyloid(1-42) decreased over time despite antiretroviral therapy containing nucleotide reverse transcriptase inhibitors.ConclusionsIn older PLWH cognitive symptoms may represent the onset of AD: a multidisciplinary team may be needed for reaching a likely in vivo diagnosis.

2021 - Author Correction: Endogenous control of inflammation characterizes pregnant women with asymptomatic or paucisymptomatic SARS-CoV-2 infection (Nature Communications, (2021), 12, 1, (4677), 10.1038/s41467-021-24940-w) [Articolo su rivista]
De Biasi, S.; Tartaro, D. L.; Gibellini, L.; Paolini, A.; Quong, A.; Petes, C.; Awong, G.; Douglas, S.; Lin, D.; Nieto, J.; Galassi, F. M.; Borella, R.; Fidanza, L.; Mattioli, M.; Leone, C.; Neri, I.; Meschiari, M.; Cicchetti, L.; Iannone, A.; Trenti, T.; Sarti, M.; Girardis, M.; Guaraldi, G.; Mussini, C.; Facchinetti, F.; Cossarizza, A.
abstract

The original version of this Article contained an error in Table 1. The correct version of the first row of the 2nd, 3rd, 5th and 7th columns states ‘CTR’, ‘PN’, ‘CTR vs PN’ and ‘PN vs PP’, instead of the original, incorrect ‘HD’, ‘NP’, ‘CTR vs NP’ and ‘CTR vs PP’. This has been corrected in both the PDF and HTML versions of the Article.

2021 - Better prognosis in females with severe COVID-19 pneumonia: possible role of inflammation as potential mediator. [Articolo su rivista]
Mussini, C; Cozzi-Lepri, A; Menozzi, M; Meschiari, M; Franceschini, E; Rogati, C; Cuomo, G; Bedini, A; Iadisernia, M; Volpi, S; Milic, J; Tonelli, R; Brugioni, L; Pietrangelo, A; Girardis, M; Cossarizza, A; Clini, E; Guaraldi, G.; De biasi, S; Gibellini, Lara
abstract

Objectives: Sex differences in COVID-19 severity and mortality have been described. Key aims of this analysis were to compare the risk of invasive mechanical ventilation (IMV) and mortality by sex and to explore whether variation in specific biomarkers could mediate this difference. Methods: This was a retrospective, observational cohort study among patients with severe COVID- 19 pneumonia. A survival analysis was conducted to compare time to the composite endpoint of IMV or death by sex. Interaction was formally tested to compare the risk difference by sex in subsets. Mediation analysis with a binary endpoint IMV or death (yes/no) by end of follow-up for a number of inflammation/coagulation biomarkers in the context of counterfactual prediction was also conducted. Results: Among 415 patients, 134 were females (32%) and 281 males (67%), median age 66 years (IQR 54-77). At admission, females showed a significantly less severe clinical and respiratory profiles with a higher PaO2/FiO2 (254 mmHg vs 191 mmHg; p=0.023). By 28 days from admission, 49.2% (95% CI: 39.6-58.9%) of males vs. 31.7% (17.9-45.4%) of females underwent IMV or death (log-rank pvalue<0.0001) and this amounted to a difference in HR of 0.40 (0.26-0.63, p=0.0001). The AUC in Creactive protein (CRP) over the study period appeared to explain 85% of this difference in risk by sex. Conclusions: Our analysis confirms a difference in the risk of COVID-19 clinical progression by sex and provides a hypothesis for potential mechanisms leading to this. CRP showed a predominant role to mediate the difference in risk by sex.

2021 - CD4/CD8 ratio in pregnant women with HIV and its association with pregnancy outcome: data from a national study in Italy [Articolo su rivista]
Floridia, Marco; Pinnetti, Carmela; Masuelli, Giulia; Spinillo, Arsenio; Savasi, Valeria M; Liuzzi, Giuseppina; Degli Antoni, Anna M; Sansone, Matilde; Guaraldi, Giovanni; Dalzero, Serena; Maso, Gianpaolo; Francisci, Daniela; Sterrantino, Gaetana; Ravizza, Marina; Tamburrini, Enrica
abstract

To evaluate associations between CD4/CD8 ratio and pregnancy outcomes in women with HIV.

2021 - Changes in central adipose tissue after switching to integrase inhibitors [Articolo su rivista]
Debroy, Paula; Feng, Han; Miao, Hongyu; Milic, Jovana; Ligabue, Guido; Draisci, Stefano; Besutti, Giulia; Carli, Federica; Menozzi, Marianna; Mussini, Cristina; Guaraldi, Giovanni; Lake, Jordan E
abstract

Background: Treatment with integrase strand transfer inhibitors (INSTIs) has been associated with excess weight gain, however the long-term effect of INSTI-based regimens on adipose tissue (AT) compartments remains unknown. Objectives: To evaluate the effect of switching to an INSTI on visceral (VAT) and subcutaneous (SAT) AT in virologically-suppressed adults with HIV. Methods: We performed a retrospective observational cohort study of ART experienced adults referred to the metabolic Clinic of the University of Modena and Reggio Emilia who had ≥2 assessments of body composition by abdominal computed tomography. An interrupted time series model with mixed-effect model incorporated was used to calculate VAT and SAT change rate, adjusting for smoking status, use of alcohol, and physical activity. Results: A total of 698 patients were included: 156 who switched to an INSTI-based regimen and 542 who did not. After switch to INSTI, mean SAT area increased approximately 3-fold (before 0.27 vs after 0.73 cm2/month; p = 0.011), and VAT area 7-fold (0.18 vs 1.30 cm2/month; p < 0.001). Conclusions: Among PLWH on ART, both SAT and VAT gain accelerated after switching to an INSTI-based regimen. The associations between INSTIs and central adiposity require further investigation.

2021 - Consensus statement on the role of health systems in advancing the long-term well-being of people living with HIV [Articolo su rivista]
Lazarus, J. V.; Safreed-Harmon, K.; Kamarulzaman, A.; Anderson, J.; Leite, R. B.; Behrens, G.; Bekker, L. -G.; Bhagani, S.; Brown, D.; Brown, G.; Buchbinder, S.; Caceres, C.; Cahn, P. E.; Carrieri, P.; Caswell, G.; Cooke, G. S.; Monforte, A. A.; Dedes, N.; del Amo, J.; Elliott, R.; El-Sadr, W. M.; Fuster-Ruiz de Apodaca, M. J.; Guaraldi, G.; Hallett, T.; Harding, R.; Hellard, M.; Jaffar, S.; Kall, M.; Klein, M.; Lewin, S. R.; Mayer, K.; Perez-Molina, J. A.; Moraa, D.; Naniche, D.; Nash, D.; Noori, T.; Pozniak, A.; Rajasuriar, R.; Reiss, P.; Rizk, N.; Rockstroh, J.; Romero, D.; Sabin, C.; Serwadda, D.; Waters, L.
abstract

Health systems have improved their abilities to identify, diagnose, treat and, increasingly, achieve viral suppression among people living with HIV (PLHIV). Despite these advances, a higher burden of multimorbidity and poorer health-related quality of life are reported by many PLHIV in comparison to people without HIV. Stigma and discrimination further exacerbate these poor outcomes. A global multidisciplinary group of HIV experts developed a consensus statement identifying key issues that health systems must address in order to move beyond the HIV field’s longtime emphasis on viral suppression to instead deliver integrated, person-centered healthcare for PLHIV throughout their lives.

2021 - Contemporary antiretrovirals and body-mass index: a prospective study of the RESPOND cohort consortium [Articolo su rivista]
Bansi-Matharu, Loveleen; Phillips, Andrew; Oprea, Cristiana; Grabmeier-Pfistershammer, Katharina; Günthard, Huldrych F; De Wit, Stephane; Guaraldi, Giovanni; Vehreschild, Jorg J; Wit, Ferdinand; Law, Matthew; Wasmuth, Jan-Christian; Chkhartishvili, Nikoloz; d'Arminio Monforte, Antonella; Fontas, Eric; Vesterbacka, Jan; Miro, Jose M; Castagna, Antonella; Stephan, Christoph; Llibre, Josep M; Neesgaard, Bastian; Greenberg, Lauren; Smith, Colette; Kirk, Ole; Duvivier, Claudine; Dragovic, Gordana; Lundgren, Jens; Dedes, Nikos; Knudsen, Andreas; Gallant, Joel; Vannappagari, Vani; Peters, Lars; Elbirt, Daniel; Sarcletti, Mario; Braun, Dominique L; Necsoi, Coca; Mussini, Cristina; Muccini, Camilla; Bolokadze, Natalie; Hoy, Jennifer; Mocroft, Amanda; Ryom, Lene
abstract

2021 - Correction to: Tocilizumab for patients with COVID-19 pneumonia. The single-arm TOCIVID-19 prospective trial (Journal of Translational Medicine, (2020), 18, 1, (405), 10.1186/s12967-020-02573-9) [Articolo su rivista]
Perrone, F.; Piccirillo, M. C.; Ascierto, P. A.; Salvarani, C.; Parrella, R.; Marata, A. M.; Popoli, P.; Ferraris, L.; Marrocco-Trischitta, M. M.; Ripamonti, D.; Binda, F.; Bonfanti, P.; Squillace, N.; Castelli, F.; Muiesan, M. L.; Lichtner, M.; Calzetti, C.; Salerno, N. D.; Atripaldi, L.; Cascella, M.; Costantini, M.; Dolci, G.; Facciolongo, N. C.; Fraganza, F.; Massari, M.; Montesarchio, V.; Mussini, C.; Negri, E. A.; Botti, G.; Cardone, C.; Gargiulo, P.; Gravina, A.; Schettino, C.; Arenare, L.; Chiodini, P.; Gallo, C.; Piccirillo, M. C.; Schettino, C.; Gravina, A.; Gargiulo, P.; Arenare, L.; Ascierto, P. A.; Vitale, M. G.; Trojaniello, C.; Palla, M.; Bianchi, A. A. M.; Botti, G.; De Feo, G.; Miscio, L.; Gallo, C.; Chiodiniy, P.; Ferraris, L.; Marrocco-Trischitta, M. M.; Froldi, M.; Menicanti, L.; Cuppone, M. T.; Gobbo, G.; Baldessari, C.; Valenti, V.; Castelvecchio, S.; Poli, F.; Giacomazzi, F.; Piccinni, R.; Annnunziata, M. L.; Biondi, A.; Bussolari, C.; Mazzoleni, M.; Giachi, A.; Filtz, A.; Manini, A.; Poletti, E.; Masserini, F.; Conforti, F.; Gaudiano, G.; Favero, V.; Moroni, A.; Viva, T.; Fancoli, F.; Ferrari, D.; Niro, D.; Resta, M.; Ballotta, A.; Poli, M. D.; Ranucci, M.; Ripamonti, D.; Binda, F.; Tebaldi, A.; Gritti, G.; Pasulo, L.; Gaglio, L.; Del Fabbro, R.; Alborghetti, L.; Giustinetti, G.; Columpsi, P.; Cazzaniga, M.; Capici, S.; Sala, L.; Di Sciacca, R.; Mosca, G.; Pirozzi, M. R.; Castelli, F.; Muiesan, M. L.; Franceschini, F.; Roccaro, A.; Salvetti, M.; Paini, A.; Corda, L.; Ricci, C.; Tomasoni, L.; Nasta, P.; Lorenzotti, S.; Odolini, S.; Foca, E.; Roldan, E. Q.; Metra, M.; Magrini, S.; Borghetti, P.; Latronico, N.; Piva, S.; Filippini, M.; Tomasi, G.; Zuccala, F.; Cattaneo, S.; Scolari, F.; Bossini, N.; Gaggiotti, M.; Properzi, M.; Lichtner, M.; Del Borgo, C.; Marocco, R.; Belvisi, V.; Tieghi, T.; De Masi, M.; Zuccala, P.; Fabietti, P.; Vetica, A.; Mercurio, V. S.; Carraro, A.; Fondaco, L.; Kertusha, B.; Curtolo, A.; Del Giudice, E.; Lubrano, R.; Zotti, M. G.; Puorto, A.; Ciuffreda, M.; Sarni, A.; Monteforte, G.; Romeo, D.; Viola, E.; Damiani, C.; Barone, A.; Mantovani, B.; Di Sanzo, D.; Gentili, V.; Carletti, M.; Aiuti, M.; Gallo, A.; Meliante, P. G.; Martellucci, S.; Riggio, O.; Cardinale, V.; Ridola, L.; Bragazzi, M. C.; Gioia, S.; Valenzi, E.; Graziosi, C.; Bina, N.; Fasolo, M.; Ricci, S.; Gioacchini, M. T.; Lucci, A.; Corso, L.; Tornese, D.; Nijhawan, P.; Equitani, F.; Cosentino, C.; Palladino, M.; Leonetti, F.; Leto, G.; Gnessi, C.; Campagna, G.; Cesareo, R.; Marrocco, F.; Straface, G.; Mecozzi, A.; Cerbo, L.; Isgro, V.; Parrocchia, S.; Visconti, G.; Casati, G.; Calzetti, C.; Ariani, A.; Donghi, L.; Salerno, N. D.; Tacconelli, E.; Bertoldi, M.; Cattaneo, P.; Lambertenghi, L.; Motta, L.; Omega, L.; Albano, G.; Parrella, R.; Fraganza, F.; Atripaldi, L.; Montesarchio, V.; Scarano, F.; De Rosa, A.; Buglione, A.; Lavoretano, S.; Gaglione, G.; De Marco, M.; Sangiovanni, V.; Fusco, F. M.; Viglietti, R.; Manzillo, E.; Rescigno, C.; Pisapia, R.; Plamieri, G.; Maraolo, A.; Calabria, G.; Catalano, M.; Fiorentino, G.; Annunziata, A.; Polistina, G.; Imitazione, P.; Mollica, M.; Esposito, V.; D'Abraccio, M.; Punzi, R.; Bianco, V.; Sbreglia, C.; Del Vecchio, R. F.; Bordonali, A.; Franco, A.; Massari, M.; Salsi, P.; Fontana, M.; Virzi, G.; Calderone, O.; Molteni, A.; Gennarini, S.; Gnudi, U.; Ricci, M. A.; Titolo, G.; Mensi, G.; Vuotto, P.; Gasperini, B.; Mancini, M.; Pasquini, Z.; Spanu, P.; Clementi, S.; Pierini, S.; Bokor, D.; Gori, D.; Ciofetti, M.; Caimi, M.; Bettazzi, L.; Allevi, E.; Furiani, S.; Capitanio, C.; Mastropasqua, B.; Fara, C.; Pulitano, G.; Matsuno, J. S.; Porta, F. D.; Dolfini, V.; Beyene, N. B.; Bezzi, M.; Novali, M.; Viale, P.; Tedeschi, S.; Pascale, R.; Bruno, R.; Di Filippo, A.; Sachs, M.; Oggionni, T.; Di Stefano, M.; Mengoli, C.; Facchini, C.; De Nardo, D.; Frausini, G.; Mucci, L.; Tedesco, S.; Girolimetti, R.; Manfredini, E.; Di Carlo, A. M.; Espinosa, E.; Dennetta, D.; Ticinesi, A.; Meschi, T.
abstract

Following publication of the original article [1] the authors identified that the collaborators of the TOCIVID-19 investigators, Italy were only available in the supplementary file. The original article has been updated so that the collaborators are correctly acknowledged. For clarity, all collaborators are listed in this correction article.

2021 - Darunavir/Cobicistat Is Associated with Negative Outcomes in HIV-Negative Patients with Severe COVID-19 Pneumonia [Articolo su rivista]
Milic, Jovana; Novella, Alessio; Meschiari, Marianna; Menozzi, Marianna; Santoro, Antonella; Bedini, Andrea; Cuomo, Gianluca; Franceschini, Erica; Digaetano, Margherita; Carli, Federica; Ciusa, Giacomo; Volpi, Sara; Bacca, Erica; Franceschi, Giacomo; Yaacoub, Dina; Rogati, Carlotta; Tutone, Marco; Burastero, Giulia; Faltoni, Matteo; Iadisernia, Vittorio; Dolci, Giovanni; Cossarizza, Andrea; Mussini, Cristina; Pasina, Luca; Guaraldi, Giovanni
abstract

The aim of this study was to evaluate both positive outcomes, including reduction of respiratory support aid and duration of hospital stay, and negative ones, including mortality and a composite of invasive mechanical ventilation or death, in patients with coronavirus disease 2019 (COVID-19) pneumonia treated with or without oral darunavir/cobicistat (DRV/c, 800/150mg/day) used in different treatment durations. The secondary objective was to evaluate the percentage of patients treated with DRV/c who were exposed to potentially severe drug-drug interactions (DDIs) and died during hospitalization. This observational retrospective study was conducted in consecutive patients with COVID-19 pneumonia admitted to a tertiary care hospital in Modena, Italy. Kaplan-Meier survival curves and Cox proportional hazards regression were used to compare patients receiving standard of care with or without DRV/c. Adjustment for key confounders was applied. Two hundred seventy-three patients (115 on DRV/c) were included, 75.8% males, mean age was 64.6 (±13.2) years. Clinical improvement was similar between the groups, depicted by respiratory aid switch (p>.05). The same was observed for duration of hospital stay [13.2 (±8.9) for DRV/c vs. 13.4 (±7.2) days for no-DRV/c, p=.9]. Patients on DRV/c had higher rates of mortality (25.2% vs. 10.1%, p<.0001. The rate of composite outcome of mechanical ventilation and death was higher in the DRV/c group (37.4% vs. 25.3%, p=.03). Multiple serious DDI associated with DRV/c were observed in the 19 patients who died. DRV/c should not be recommended as a treatment option for COVID-19 pneumonia outside clinical trials.

2021 - Determinants of loss to care and risk of clinical progression in PLWH who are re-engaged in care after a temporary loss [Articolo su rivista]
Mussini, Cristina; Lorenzini, Patrizia; Cozzi-Lepri, Alessandro; Mammone, Alessia; Guaraldi, Giovanni; Marchetti, Giulia; Lichtner, Miriam; Lapadula, Giuseppe; Lo Caputo, Sergio; Antinori, Andrea; d'Arminio Monforte, Antonella; Girardi, Enrico
abstract

The risk of developing AIDS is elevated not only among those with a late HIV diagnosis but also among those lost to care (LTC). The aims were to address the risk of becoming LTC and of clinical progression in LTC patients who re-enter care. Patients were defined as LTC if they had no visit for ≥ 18 months. Of these, persons with subsequent visits were defined as re-engaged in care (RIC). Factors associated with becoming LTC and RIC were investigated. The risk of disease progression was estimated by comparing RIC with patients continuously followed. Over 11,285 individuals included, 3962 became LTC, and of these, 1062 were RIC. Older age, presentation with AIDS and with higher HIV-RNA were associated with a reduced risk of LTC. In contrast, lower education level, irregular job, being an immigrant and injecting-drug user were associated with an increased LTC probability. Moreover, RIC with HIV-RNA > 200 copies/mL at the re-entry had a higher risk of clinical progression, while those with HIV-RNA ≤ 200 copies/mL had a higher risk of only non-AIDS progression. Patients re-entering care after being LTC appeared to be at higher risk of clinical progression than those continuously in care. Active strategies for re-engagement in care should be promoted.

2021 - Development and validation of a prediction model for tocilizumab failure in hospitalized patients with SARS-CoV-2 infection [Articolo su rivista]
Mussini, C; Cozzi-Lepri, A; Menozzi, M; Meschiari, M; Franceschini, E; Milic, J; Brugioni, L; Pietrangelo, A; Girardis, M; Cossarizza, A; Tonelli, R; Clini, E; Massari, M; Bartoletti, M; Ferrari, A; Cattelan, Am; Zuccalà, P; Lichtner, M; Rossotti, R; Girardi, E; Nicastri, E; Puoti, M; Antinori, A; Viale, Pl; Guaraldi, G.
abstract

Background: The aim of this secondary analysis of the TESEO cohort is to identify, early in the course of treatment with tocilizumab, factors associated with the risk of progressing to mechanical ventilation and death and develop a risk score to estimate the risk of this outcome according to patients’ profile. Methods: Patients with COVID-19 severe pneumonia receiving standard of care + tocilizumab who were alive and free from mechanical ventilation at day6 after treatment initiation were included in this retrospective, multicenter cohort study. Multivariable logistic regression models were built to identify predictors of mechanical ventilation or death by day-28 from treatment initiation and β-coefficients were used to develop a risk score. Secondary outcome was mortality. Patients with the same inclusion criteria as the derivation cohort from 3 independent hospitals were used as validation cohort. Results: 266 patients treated with tocilizumab were included. By day 28 of hospital follow-up post treatment initiation, 40 (15%) underwent mechanical ventilation or died [26 (10%)]. At multivariable analysis, sex, day-4 PaO2/FiO2 ratio, platelets and CRP were independently associated with the risk of developing the study outcomes and were used to generate the proposed risk score. The accuracy of the score in AUC was 0.80 and 0.70 in internal validation and test for the composite endpoint and 0.92 and 0.69 for death, respectively. Conclusions: Our score could assist clinicians in identifying, early after tocilizumab, patients who are likely to progress to mechanical ventilation or death so that they could be selected for eventual rescue therapies.

2021 - Development of post-COVID-19 cardiovascular events: An analysis of clinical features and risk factors from a single hospital retrospective study [Articolo su rivista]
Cuomo, G.; Puzzolante, C.; Iadisernia, V.; Santoro, A.; Menozzi, M.; Carli, F.; Digaetano, M.; Orlando, G.; Franceschini, E.; Bedini, A.; Meschiari, M.; Manzini, L.; Corradi, L.; Milic, J.; Borghi, V.; Brugioni, L.; Pietrangelo, A.; Clini, E.; Girardis, M.; Guaraldi, G.; Mussini, C.
abstract

Cardiovascular complications after a SARS-CoV-2 infection are a phenomenon of relevant scientific inter-est. The aim of this study was to analyze the onset of post-COVID-19 cardiovascular events in patients hospitalized in a tertiary care center. This is a retrospective study conducted on patients hospitalized over a period of three months. The patients were older than 18 years of age and had a diagnosis of COVID-19 infection confirmed from a nasopharyngeal swab sample. Anamnestic and clinical-laboratory data were collected. Cardiovascular events at 30 days were defined as follows: arrhythmias, myocardial infarction, myocarditis, and pulmonary embolism. Univariate analysis (Student’s t-test or Mann-Whitney U test, as appropriate) and multivariate analysis (multinomial logistic regression) were applied to the data. A total of 394 patients were included; they were mostly males and had a median age of 65.5 years. Previous cardiovascular disease was present in 14.7% of patients. Oxygen therapy was required for 77.9%, and 53% received anticoagulant therapy. The overall 30-day mortality was 20.3%. A cardiovascular event developed in 15.7% of the subjects. These were mainly pulmonary embolism (9.4%), followed by arrhythmias (3.3%), myocardial infarction (2.3%), and myocarditis (0.8%). Patients who developed cardiovascular events upon univariate analysis were significantly older, with major comorbidities, a more compromised respiratory situation, and a higher mortality rate. Multivariate analysis revealed independent factors that were significantly associated with the development of cardiovascular events: hypertension, endotracheal intubation, and age older than 75 years. In patients with COVID-19, the development of a cardiovascular event occurs quite frequently and is mainly seen in elderly subjects with comorbidities (especially hypertension) in the presence of a severe respiratory picture.

2021 - Disentangling the association of hydroxychloroquine treatment with mortality in covid-19 hospitalized patients through hierarchical clustering [Articolo su rivista]
Di Castelnuovo, A.; Gialluisi, A.; Antinori, A.; Berselli, N.; Blandi, L.; Bonaccio, M.; Bruno, R.; Cauda, R.; Costanzo, S.; Guaraldi, G.; Menicanti, L.; Mennuni, M.; My, I.; Parruti, G.; Patti, G.; Perlini, S.; Santilli, F.; Signorelli, C.; Stefanini, G.; Vergori, A.; Ageno, W.; Agodi, A.; Agostoni, P.; Aiello, L.; Moghazi, S. A.; Arboretti, R.; Aucella, F.; Barbieri, G.; Barchitta, M.; Bonfanti, P.; Cacciatore, F.; Caiano, L.; Cannata, F.; Carrozzi, L.; Cascio, A.; Castiglione, G.; Cicullo, A.; Cingolani, A.; Cipollone, F.; Colomba, C.; Colombo, C.; Crisetti, A.; Crosta, F.; Danzi, G. B.; D'Ardes, D.; de Gaetano Donati, K.; Di Gennaro, F.; Di Tano, G.; D'Offizi, G.; Fusco, F. M.; Gaudiosi, C.; Gentile, I.; Gianfagna, F.; Giuliano, G.; Graziani, E.; Guarnieri, G.; Langella, V.; Larizza, G.; Leone, A.; Maccagni, G.; Magni, F.; Maitan, S.; Mancarella, S.; Manuele, R.; Mapelli, M.; Maragna, R.; Marcucci, R.; Maresca, G.; Marongiu, S.; Marotta, C.; Marra, L.; Mastroianni, F.; Mengozzi, A.; Meschiari, M.; Milic, J.; Minutolo, F.; Mussinelli, R.; Mussini, C.; Musso, M.; Odone, A.; Olivieri, M.; Palimodde, A.; Pasi, E.; Pesavento, R.; Petri, F.; Pivato, C. A.; Poletti, V.; Ravaglia, C.; Righetti, G.; Rognoni, A.; Rossato, M.; Rossi, I.; Rossi, M.; Sabena, A.; Salinaro, F.; Sangiovanni, V.; Sanrocco, C.; Moriello, N. S.; Scorzolini, L.; Sgariglia, R.; Simeone, P. G.; Spinicci, M.; Tamburrini, E.; Torti, C.; Trecarichi, E. M.; Vettor, R.; Vianello, A.; Vinceti, M.; Virdis, A.; de Caterina, R.; Iacoviello, L.
abstract

The efficacy of hydroxychloroquine (HCQ) in treating SARS-CoV-2 infection is harshly debated, with observational and experimental studies reporting contrasting results. To clarify the role of HCQ in Covid-19 patients, we carried out a retrospective observational study of 4,396 unselected patients hospitalized for Covid-19 in Italy (February–May 2020). Patients’ characteristics were collected at entry, including age, sex, obesity, smoking status, blood parameters, history of diabetes, cancer, cardiovascular and chronic pulmonary diseases, and medications in use. These were used to identify subtypes of patients with similar characteristics through hierarchical clustering based on Gower distance. Using multivariable Cox regressions, these clusters were then tested for association with mortality and modification of effect by treatment with HCQ. We identified two clusters, one of 3,913 younger patients with lower circulating inflammation levels and better renal function, and one of 483 generally older and more comorbid subjects, more prevalently men and smokers. The latter group was at increased death risk adjusted by HCQ (HR [CI95%] = 3.80[3.08-4.67]), while HCQ showed an independent inverse association (0.51[0.43-0.61]), as well as a significant influence of cluster∗HCQ interaction (p < 0.001). This was driven by a differential association of HCQ with mortality between the high (0.89[0.65-1.22]) and the low risk cluster (0.46[0.39-0.54]). These effects survived adjustments for additional medications in use and were concordant with associations with disease severity and outcome. These findings suggest a particularly beneficial effect of HCQ within low risk Covid-19 patients and may contribute to clarifying the current controversy on HCQ efficacy in Covid-19 treatment.

2021 - Dolutegravir is not associated with weight gain in ART experienced geriatric patients living with HIV [Articolo su rivista]
Guaraldi, Giovanni; Calza, Stefano; Milic, Jovana; Calcagno, Andrea; Focà, Emanuele; Rota, Matteo; Renzetti, Stefano; Celotti, Anna; Siano, Matteo; Celesia, Benedetto Maurizio; Piconi, Stefania; de Socio, Giuseppe Vittorio; Cattelan, Anna Maria; Orofino, Giancarlo; Riva, Agostino; Nozza, Silvia; di Perri, Giovanni
abstract

OBJECTIVE: The aim of this study was to explore weight gain (WG) in people living with HIV (PLWH) ≥65 years who switch to a DTG based regimen (DTG-s) vs remaining INSTI-naive (INSTI-n) on stable ART.METHODS: This was a longitudinal prospective study of PLWH from the GEPPO cohort. At the beginning of the observational period, participants were INSTI-naives (INSTI-n). During follow-up, they were divided in two groups: INSTI-n vs dolutegravir-switchers (DTG-s) with no further change in ART. Body weight was assessed at baseline and at last follow-up visit. Significant weight gain was defined as an increase ≥5% of baseline weight from the first to the last visit. ART regimens were collected at each patients' visit. Kaplan-Meier curves were drawn to assess time to reach a WG >5%.RESULTS: Out of 568 PLWH (83.1% males, median age 69.5 years), 427 (75%) were INSTI-n and 141 (25%) DTG-s. After an average follow-up of 2.6 (±0.8) years, no significant change in body weight was observed both among INSTI-n (delta weight=0.02 (±7.5), p=0.633) and DTG-s (delta weight= -0.04 (±5.2), p=0.755). WG was also not significantly different between study groups (9.3% in INSTI-n and 15.1% in DTG-S: p = 0.175). No significant differences in time to achieve a WG greater or equal than 5% of baseline weight emerged in INSTI-n vs DTG-s (p = 0.93), two-drug regimens (2DR) vs three-drug regimens (3DR) (p = 0.56) or TAF vs TDF (p = 0.56).CONCLUSIONS: Results from a large Italian cohort did not show a significant WG associated with switch to DTG in PLWH 65 years of age or older. This finding emerged also when comparing 3DR vs 2DR and TAF exposed and unexposed geriatric PLWH.

2021 - Durability of Integrase STrand Inhibitor (InSTI)-based regimen in geriatric people living with HIV in the GEPPO cohort [Articolo su rivista]
Foca, E.; Calcagno, A.; Calza, S.; Renzetti, S.; Chiesa, A.; Siano, M.; de Socio, G.; Piconi, S.; Orofino, G.; Madeddu, G.; Cattelan, A. M.; Nozza, S.; Ferrara, M.; Milic, J.; Celesia, B. M.; Castelli, F.; Guaraldi, G.
abstract

Objective To investigate the durability of the first integrase inhibitor-based regimen in a HIV geriatric multicentric prospective cohort and to explore the reasons of regimen discontinuation. Design This is an analysis conducted on the Geriatric Patients Living with HIV/AIDS (GEPPO) cohort, an Italian prospective observational multicentre cohort of people living with HIV with 65 years of age or more. Methods The analysis was performed using R (version 4.0.2). The tests performed were two sided assuming a 5% significance level (Kruskal-Wallis test, Chi-squared test, log-rank test and a Cox Proportional Hazard model). The proportion of participants discontinuing the three regimens was displayed using cumulative curves. Results Among 1531 patients enrolled between 2017 and 2019 in the GEPPO cohort, we included 822 participants in this analysis. At baseline, median age was 69.8, the immunovirological profile good, multimorbidity was present in 42.3% of participants, while 27.4% were on polypharmacy. Overall, 483, 243 and 96 participants received DTG, RAL and EVG/c respectively as first InSTI. At the end of the follow up 6.4%, 21.1% and 22.9% participants discontinued DTG, RAL and EVG/c respectively. Using a log-rank test, EVG showed a significantly lower durability than DTG (p<0.001) or RAL (p 0.05) or both, DTG and RAL (p<0.001). Among participants who discontinued their regimen we found 0 virological failure and 56.7% simplification/deprescription. Conclusions The three integrase inhibitors considered showed a good durability and no virological failures in geriatric patients such as those enrolled in the GEPPO cohort when used in a two or three drug regimen.

2021 - Effects of cytokine blocking agents on hospital mortality in patients admitted to ICU with acute respiratory distress syndrome by SARS-CoV2 infection: retrospective cohort study. [Articolo su rivista]
Coloretti, I; Busani, S; Biagioni, E; Venturelli, S; Munari, E; Marco, S; Dall’Ara, L; Tosi, M; Clini, E; Tonelli, R; Fantini, R; Mussini, C; Meschiari, M; Guaraldi, G; Cossarizza, A; Alfano, G; Girardis, M; Gibellini, Lara
abstract

Background- The use of cytokine-blocking agents has been proposed to modulate the inflammatory response in patients with COVID19. Tocilizumab and Anakinra were included in the local protocol as an optional treatment in critically ill patients with acute respiratory distress syndrome (ARDS) by SARS-CoV2 infection. This cohort study evaluated the effects of therapy with cytokine blocking agents on in-hospital mortality in COVID19 patients requiring mechanical ventilation and admitted to intensive care unit. Methods- The association between therapy with Tocilizumab or Anakinra and in-hospital mortality was assessed in consecutive adult COVID19 patients admitted to our ICU with moderate to severe ARDS. The association was evaluated by comparing patients who receive to those who did not receive Tocilizumab or Anakinra and by using different multivariable Cox models adjusted for variables related to poor outcome, for the propensity to be treated with Tocilizumab or Anakinra and after patient matching. Results- Sixty-six patients who received immunotherapy (49 Tocilizumab, 17 Anakinra) and 28 patients who did not receive immunotherapy were included. The in-hospital crude mortality was 30,3% in treated patients and 50% in non-treated (OR 0,77, 95% CI 0,56-1,05, p=0,069). The adjusted Cox model showed an association between therapy with immunotherapy and in-hospital mortality (HR 0,40, 95% CI 0,19-0,83, p=0,015). This protective effect was further confirmed in the analysis adjusted for propensity score, in the propensity-matched cohort and in the cohort of patients with invasive mechanical ventilation within 2 hours after ICU admission. Conclusions- Although important limitations, our study showed that cytokine-blocking agents seem to be safe and to improve survival in COVID-19 patients admitted to ICU with ARDS and the need of mechanical ventilation.

2021 - Endogenous control of inflammation characterizes pregnant women with asymptomatic or paucisymptomatic SARS-CoV-2 infection [Articolo su rivista]
De Biasi, S.; Tartaro, D. L.; Gibellini, L.; Paolini, A.; Quong, A.; Petes, C.; Awong, G.; Douglas, S.; Lin, D.; Nieto, J.; Galassi, F. M.; Borella, R.; Fidanza, L.; Mattioli, M.; Leone, C.; Neri, I.; Meschiari, M.; Cicchetti, L.; Iannone, A.; Trenti, T.; Sarti, M.; Girardis, M.; Guaraldi, G.; Mussini, C.; Facchinetti, F.; Cossarizza, A.
abstract

SARS-CoV-2 infection can affect all human beings, including pregnant women. Thus, understanding the immunological changes induced by the virus during pregnancy is nowadays of pivotal importance. Here, using peripheral blood from 14 pregnant women with asymptomatic or mild SARS-CoV-2 infection, we investigate cell proliferation and cytokine production, measure plasma levels of 62 cytokines, and perform a 38-parameter mass cytometry analysis. Our results show an increase in low density neutrophils but no lymphopenia or gross alterations of white blood cells, which display normal levels of differentiation, activation or exhaustion markers and show well preserved functionality. Meanwhile, the plasma levels of anti-inflammatory cytokines such as interleukin (IL)-1RA, IL-10 and IL-19 are increased, those of IL-17, PD-L1 and D-dimer are decreased, but IL-6 and other inflammatory molecules remain unchanged. Our profiling of antiviral immune responses may thus help develop therapeutic strategies to avoid virus-induced damages during pregnancy.

2021 - Erratum: The Role of the Renin-Angiotensin System in Severe Acute Respiratory Syndrome-CoV-2 Infection (Journal of Physical Chemistry DOI: 10.1159/000507914) [Articolo su rivista]
Alfano, G.; Guaraldi, G.; Fontana, F.; Ferrari, A.; Magistroni, R.; Mussini, C.; Cappelli, G.
abstract

In the article by Alfano et al. entitled “The Role of the Renin-Angiotensin System in Severe Acute Respiratory Syndrome-CoV-2 Infection” [Blood Purif. DOI: 10.1159/000507914], the affiliations should be indicated as follows:.

2021 - Geriatric Syndromes in People Living with HIV Associated with Ageing and Increasing Comorbidities: Implications for Neurocognitive Complications of HIV Infection [Capitolo/Saggio]
Falutz, Julian; Kirkland, Susan; Guaraldi, Giovanni
abstract

Long-term survival of treated people living with HIV (PLWH) currently approaches that of the general population. The average age of PLWH is currently in the mid-50s in resource-rich countries and is predicted that over 40% of PLWH will be older than 60 within a decade. Similar trends have been confirmed in all communities of PLWH with access to antiretroviral therapies. However, the positive impact on survival has been challenged by several developments. Ageing PLWH have clinical features similar to the general population about 5-10 years older. In addition to the earlier occurrence of common age-related conditions common geriatric syndromes have also impacted this population prematurely. These are often difficult to evaluate and manage conditions usually of multifactorial aetiology. They include polypharmacy, frailty, impaired mobility and falls, sarcopenia, sensory impairment, and increasingly, non-dementing cognitive decline. Cognitive decline is of particular concern to PLWH and their care providers. In the general geriatric population cognitive impairment increases with age and occurs in all populations with a prevalence of over 25% in people over 80. Effective treatments are lacking and therefore minimizing risk factors plays an important role in maintaining healthspan. In the general population geriatric syndromes may increase the risk of cognitive decline. The corollary is that decreasing the risk of their development may limit cognitive impairment. Whether a similar status holds in PLWH is uncertain. This chapter will address the question of whether common geriatric syndromes in PLWH contribute to cognitive impairment. Common risk factors may provide clues to limit or delay cognitive decline.

2021 - Has COVID-19 changed the approach to HIV diagnosis?: A multicentric Italian experience [Articolo su rivista]
Mazzitelli, Maria; Ciccullo, Arturo; Baldin, Gianmaria; Cauda, Roberto; Rusconi, Stefano; Giacomelli, Andrea; Oreni, Letizia; Borghi, Vanni; Mussini, Cristina; Guaraldi, Giovanni; Sterrantino, Gaetana; Lagi, Filippo; Candelaresi, Bianca; Cirioni, Oscar; De Vito, Andrea; Rossetti, Barbara; Torti, Carlo; Di Giambenedetto, Simona
abstract

The occurrence of COVID-19 pandemic had a significant negative effect on health care systems over the last year. Health care providers were forced to focus mainly on COVID-19 patients, neglecting in many cases equally important diseases, both acute and chronic. Therefore, also screening and diagnostic strategies for HIV could have been significantly impaired.This retrospective, multicenter, observational study aimed at assessing the number and characteristics of new HIV/AIDS diagnoses during COVID-19 pandemic in Italy and compared characteristics of people living with HIV at diagnosis between pre- and post-COVID-19 era (2019 vs 2020).Our results showed a significant reduction of HIV diagnoses during pandemic. By contrast, people living with HIV during pandemic were older and were diagnosed in earlier stage of disease (considering CD4+ T cell count) compared to those who were diagnosed the year before. Moreover, there was a significant decrease of new HIV diagnoses among men who have sex with men, probably for the impact of social distancing and restriction applied by the Italian Government. Late presentation incidence, if numbers in 2020 were lower than those in 2019, is still an issue.Routinely performing HIV testing in patients with suspected SARS-CoV-2 infection is identifying and linking to care underdiagnosed people living with HIV earlier. Thus, combined tests (HIV and SARS-CoV-2) should be implemented in patients with SARS-CoV-2 symptoms overlapping HIV's ones. Lastly, our results lastly showed how urgent implementation of a national policy for HIV screening is necessary.

2021 - Health status is related to testosterone, estrone and body fat: moving to functional hypogonadism in adult men with HIV. [Articolo su rivista]
De Vincentis, S.; Decaroli, M. C.; Fanelli, F.; Diazzi, C.; Mezzullo, M.; Morini, F.; Bertani, D.; Milic, J.; Carli, F.; Cuomo, G.; Santi, D.; Tartaro, G.; Tagliavini, S.; De Santis, M. C.; Roli, L.; Trenti, T.; Pagotto, U.; Guaraldi, G.; Rochira, V.
abstract

Objective: Hypogonadism is common in HIV-infected men. The relationship between health status, sex steroids and body composition is poorly known in HIV. The aim was to investigate the association between health status (comorbidities/frailty), body composition, and gonadal function in young-to-middle-aged HIV-infected men. Design: Prospective, cross-sectional, observational study. Methods: HIV-infected men aged<50 years and ongoing Highly Active Antiretroviral Therapy were enrolled. Serum total testosterone (TT), estradiol (E2), estrone (E1) were measured by liquid chromatography-tandem mass spectrometry, LH and FSH by immunoassay. Free testosterone (cFT) was calculated by Vermeulen equation. Body composition was assessed by dual-energy X-ray absorptiometry and abdominal CT scan. Multimorbidity (MM) and frailty were defined as ≥3 comorbidities and by a 37-item index, respectively. Results: A total of 316 HIV-infected men aged 45.3±5.3 years were enrolled. Body fat parameters were inversely related to cFT and TT, and directly related to E1 and E2/T ratio. Patients with MM had lower cFT (p<0.0001) and TT (p=0.036), and higher E1 (p<0.0001) and E2/T ratio (p=0.002). Frailty was inversely related to cFT (R2=0.057, p<0.0001) and TT (R2=0.013, p=0.043), and directly related to E1 (R2=0.171, p<0.0001), E2 (R2=0.041, p=0.004) and E2/T ratio (R2=0.104, p<0.0001). Conclusions: Lower TT and cFT, higher E1, E2/T ratio and visceral fat were independently associated to poor health status and frailty, being possible hallmarks of unhealthy conditions in adult HIV-infected men. Overall, MM, frailty and body fat mass are strictly associated to each other and to sex steroids, concurring together to functional male hypogonadism in HIV.

2021 - HelpCOVID [Software]
Guaraldi, Giovanni
abstract

Sito internet che offre un servizio di counselling online con lo scopo di offrire nuovi punti di incontro tra l’utente e l’operatore sanitario. HelpCOVID è un progetto che nasce dalla necessità di fare chiarezza in un momento in cui la popolazione è esposta ogni giorno a notizie provenienti da fonti diverse, e a volte fuorvianti. La mission di HelpCOVID è di avvicinare gli utenti all'informazione affidabile, utilizzando però un linguaggio semplice, comprensibile, ma comunque preciso e affidabile. Ogni affermazione è supportata da articoli scientifici, oppure e è tratta dalle linee Linee Guida istituzionali.

2021 - Heparin in COVID-19 Patients Is Associated with Reduced In-Hospital Mortality: The Multicenter Italian CORIST Study [Articolo su rivista]
Di Castelnuovo, A.; Costanzo, S.; Antinori, A.; Berselli, N.; Blandi, L.; Bonaccio, M.; Cauda, R.; Guaraldi, G.; Menicanti, L.; Mennuni, M.; Parruti, G.; Patti, G.; Santilli, F.; Signorelli, C.; Vergori, A.; Abete, P.; Ageno, W.; Agodi, A.; Agostoni, P.; Aiello, L.; Al Moghazi, S.; Arboretti, R.; Astuto, M.; Aucella, F.; Barbieri, G.; Bartoloni, A.; Bonfanti, P.; Cacciatore, F.; Caiano, L.; Carrozzi, L.; Cascio, A.; Ciccullo, A.; Cingolani, A.; Cipollone, F.; Colomba, C.; Colombo, C.; Crosta, F.; Danzi, G. B.; D'Ardes, D.; De Gaetano Donati, K.; Di Gennaro, F.; Di Tano, G.; D'Offizi, G.; Fantoni, M.; Fusco, F. M.; Gentile, I.; Gianfagna, F.; Grandone, E.; Graziani, E.; Grisafi, L.; Guarnieri, G.; Larizza, G.; Leone, A.; Maccagni, G.; Madaro, F.; Maitan, S.; Mancarella, S.; Mapelli, M.; Maragna, R.; Marcucci, R.; Maresca, G.; Marongiu, S.; Marotta, C.; Marra, L.; Mastroianni, F.; Mazzitelli, M.; Mengozzi, A.; Menichetti, F.; Meschiari, M.; Milic, J.; Minutolo, F.; Molena, B.; Montineri, A.; Mussini, C.; Musso, M.; Niola, D.; Odone, A.; Olivieri, M.; Palimodde, A.; Parisi, R.; Pasi, E.; Pesavento, R.; Petri, F.; Pinchera, B.; Poletti, V.; Ravaglia, C.; Rognoni, A.; Rossato, M.; Rossi, M.; Sangiovanni, V.; Sanrocco, C.; Scorzolini, L.; Sgariglia, R.; Simeone, P. G.; Taddei, E.; Torti, C.; Vettor, R.; Vianello, A.; Vinceti, M.; Virano, A.; Vocciante, L.; De Caterina, R.; Iacoviello, L.
abstract

Introduction A hypercoagulable condition was described in patients with coronavirus disease 2019 (COVID-19) and proposed as a possible pathogenic mechanism contributing to disease progression and lethality. Aim We evaluated if in-hospital administration of heparin improved survival in a large cohort of Italian COVID-19 patients. Methods In a retrospective observational study, 2,574 unselected patients hospitalized in 30 clinical centers in Italy from February 19, 2020 to June 5, 2020 with laboratory-confirmed severe acute respiratory syndrome coronavirus-2 infection were analyzed. The primary endpoint in a time-to event analysis was in-hospital death, comparing patients who received heparin (low-molecular-weight heparin [LMWH] or unfractionated heparin [UFH]) with patients who did not. We used multivariable Cox proportional-hazards regression models with inverse probability for treatment weighting by propensity scores. Results Out of 2,574 COVID-19 patients, 70.1% received heparin. LMWH was largely the most used formulation (99.5%). Death rates for patients receiving heparin or not were 7.4 and 14.0 per 1,000 person-days, respectively. After adjustment for propensity scores, we found a 40% lower risk of death in patients receiving heparin (hazard ratio = 0.60; 95% confidence interval: 0.49-0.74; E-value = 2.04). This association was particularly evident in patients with a higher severity of disease or strong coagulation activation. Conclusion In-hospital heparin treatment was associated with a lower mortality, particularly in severely ill COVID-19 patients and in those with strong coagulation activation. The results from randomized clinical trials are eagerly awaited to provide clear-cut recommendations.

2021 - Herpes Simplex re-activation in patients with SARS-CoV2 pneumonia: a prospective observational study. [Articolo su rivista]
Franceschini, E; Cozzi-Lepri, A; Santoro, A; Bacca, E; Lancellotti, G; Menozzi, M; Gennari, W; Meschiari, M; Bedini, A; Orlando, G; Puzzolante, C; Digaetano, M; Milic, J; Codeluppi, M; Pecorari, M; Carli, F; Cuomo, G; Alfano, G; Corradi, L; Tonelli, R; De Maria, N; Busani, S; Biagioni, E; Coloretti, I; Guaraldi, G; Sarti, M; Luppi, M; Clini, E; Girardis, M; Gyssens, I; Mussini, C.
abstract

Background: Herpes simplex 1 co-infections in patients with COVID-19 are considered relatively uncommon; some reports on re-activations in patients in intensive-care unit have been published. The aim of the study was to analyze herpetic re-activations and their clinical manifestations in hospitalized COVID-19 patients, performing HSV-1 PCR on plasma twice a week. Methods: We conducted a prospective, observational, single-center study involving 70 consecutive patients with severe/critical SARS-CoV-2 pneumonia tested for HSV-1 hospitalized at Azienda Ospedaliero-Universitaria of Modena. Results: Of these 70 patients, 21 (30.0%) showed detectable viremia and 13 (62%) had clinically relevant manifestations of HSV-1 infection corresponding to 15 events (4 pneumonia, 5 herpes labialis, 3 gingivostomatitis, one encephalitis and two hepatitis). HSV-1 positive patients were more frequently treated with steroids than HSV-1 negative patients (76.2% vs 49.0%, p 0.036) and more often underwent mechanical ventilation (IMV) (57.1% vs 22.4%, p 0.005). In the unadjusted logistic regression analysis, steroid treatment, IMV, and higher LDH were significantly associated with an increased risk of HSV1 re-activation (odds ratio 3.33, 4.61, and 16.9, respectively). The association with use of steroids was even stronger after controlling for previous use of both tocilizumab and IMV (OR=5.13, 95% CI:1.36-19.32, p=0.016). The effect size was larger when restricting to participants who were treated with high dose of steroids while there was no evidence to support an association with use of tocilizumab. Conclusions: Our study shows a high incidence of HSV-1 reactivation both virologically and clinically in patients with SARS-CoV-51 2 severe pneumonia, especially in those treated with steroids.

2021 - Human Immunodeficiency Virus (HIV) Care Models During the Coronavirus Disease 2019 (COVID-19) Era [Articolo su rivista]
Guaraldi, Giovanni; Milic, Jovana; Martinez, Esteban; Kamarulzaman, Adeeba; Mussini, Cristina; Waters, Laura; Pozniak, Anton; Mallon, Patrick; Rockstroh, Jürgen; Lazarus, Jeffrey V
abstract

The COVID-19 pandemic is an unprecedented global challenge that substantially risks reversing the progress in ending HIV. At the same time, it may offer the opportunity for a new era of HIV management. This viewpoint presents the impact of COVID-19 on HIV care, including the Joint United Nations Programme on HIV/AIDS (UNAIDS) "three 90s" targets. It outlines how to enhance a patient-centered care approach, now known as the "fourth 90," by integrating face-to-face patient-physician and telemedicine encounters. It suggests a framework for prevention and treatment of multimorbidity and frailty, to achieve a good health-related quality of life and preserve intrinsic capacity in all people living with HIV.

2021 - Hypokalemia in Patients with COVID-19 [Articolo su rivista]
Alfano, G.; Ferrari, A.; Fontana, F.; Perrone, R.; Mori, G.; Ascione, E.; Magistroni, R.; Venturi, G.; Pederzoli, S.; Margiotta, G.; Romeo, M.; Piccinini, F.; Franceschi, G.; Volpi, S.; Faltoni, M.; Ciusa, G.; Bacca, E.; Tutone, M.; Raimondi, A.; Menozzi, M.; Franceschini, E.; Cuomo, G.; Orlando, G.; Santoro, A.; Di Gaetano, M.; Puzzolante, C.; Carli, F.; Bedini, A.; Milic, J.; Meschiari, M.; Mussini, C.; Cappelli, G.; Guaraldi, G.; Borghi, V.; Burastero, G.; Corradi, L.; Di Gaetano, M.; Dolci, G.; Fantini, R.; Iadisernia, V.; Larne, D.; Pellegrino, F.; Rogati, C.; Santoro, A.; Tonelli, R.; Yaacoub, D.; Alfan, S.; Marco, B.; Pulizzi, R.; Leonelli, M.; Facchini, F.; Damiano, F.; Girardis, M.; Andreotti, A.; Biagioni, E.; Bondi, F.; Busani, S.; Chierego, G.; Scotti, M.; Cossarizza, L. S. A.; Bellinazzi, C.; Borella, R.; De Biasi, S.; De Gaetano, A.; Fidanza, L.; Gibellini, L.; Iannone, A.; Tartaro, D. L.; Mattioli, M.; Nasi, M.; Paolini, A.; Pinti, M.
abstract

Background: Patients with COVID-19 experience multiple clinical conditions that may cause electrolyte imbalances. Hypokalemia is a concerning electrolyte disorder closely associated with severe complications. This study aimed to estimate prevalence, risk factors and outcome of hypokalemia in a cohort of patients with confirmed COVID-19. Methods: A retrospective analysis was conducted on 290 non-ICU admitted patients with COVID-19 at the tertiary teaching hospital of Modena, Italy, from February 16 to April 14, 2020. Results: Hypokalemia was detected in 119 out of 290 patients (41%) during hospitalization. Mean serum potassium was 3.1 ± 0.1 meq/L. The majority of patients (90.7%) patients experienced only a mild decrease in serum potassium level (3–3.4 mEq/L). Hypokalemia was associated with hypocalcemia, which was detected in 50% of subjects. Urine potassium-to-creatinine ratio, measured in a small number of patients (n = 45; 36.1%), revealed an increase of urinary potassium excretion in most cases (95.5%). Risk factors for hypokalemia were female sex (odds ratio (OR) 2.44; 95% CI 1.36–4.37; P 0.003) and diuretic therapy (OR 1.94, 95% CI 1.08–3.48; P 0.027). Hypokalemia, adjusted for sex, age and SOFA score, was not associated with ICU transfer (OR 0.52; 95% CI 0.228–1.212; P = 0.131), in-hospital mortality (OR, 0.47; 95% CI 0.170–1.324; P = 0.154) and composite outcome of ICU transfer or in-hospital mortality (OR 0.48; 95% CI 0.222–1.047; P = 0.065) in our cohort of patients. Conclusions: Hypokalemia was a frequent disorder in subjects with COVID-19. Female sex and diuretic therapy were identified as risk factors for low serum potassium levels. Hypokalemia was unrelated to ICU transfer and death in this cohort of patients.

2021 - Identification and characterization of a SARS-CoV-2 specific CD8+ T cell response with immunodominant features [Articolo su rivista]
Gangaev, Anastasia; Ketelaars, Steven L C; Isaeva, Olga I; Patiwael, Sanne; Dopler, Anna; Hoefakker, Kelly; De Biasi, Sara; Gibellini, Lara; Mussini, Cristina; Guaraldi, Giovanni; Girardis, Massimo; Ormeno, Cami M P Talavera; Hekking, Paul J M; Lardy, Neubury M; Toebes, Mireille; Balderas, Robert; Schumacher, Ton N; Ovaa, Huib; Cossarizza, Andrea; Kvistborg, Pia
abstract

The COVID-19 pandemic caused by SARS-CoV-2 is a continuous challenge worldwide, and there is an urgent need to map the landscape of immunogenic and immunodominant epitopes recognized by CD8+ T cells. Here, we analyze samples from 31 patients with COVID-19 for CD8+ T cell recognition of 500 peptide-HLA class I complexes, restricted by 10 common HLA alleles. We identify 18 CD8+ T cell recognized SARS-CoV-2 epitopes, including an epitope with immunodominant features derived from ORF1ab and restricted by HLA-A*01:01. In-depth characterization of SARS-CoV-2-specific CD8+ T cell responses of patients with acute critical and severe disease reveals high expression of NKG2A, lack of cytokine production and a gene expression profile inhibiting T cell re-activation and migration while sustaining survival. SARS-CoV-2-specific CD8+ T cell responses are detectable up to 5 months after recovery from critical and severe disease, and these responses convert from dysfunctional effector to functional memory CD8+ T cells during convalescence.

2021 - Immunosuppressive therapy reduction and early post-infection graft function in kidney transplant recipients with COVID-19 [Articolo su rivista]
Alfano, Gaetano; Damiano, Francesca; Fontana, Francesco; Ferri, Camilla; Melluso, Andrea; Montani, Martina; Morisi, Niccolò; Tei, Lorenzo; Plessi, Jessica; Giovanella, Silvia; Ligabue, Giulia; Mori, Giacomo; Guaraldi, Giovanni; Magistroni, Riccardo; Cappelli, Gianni; Donati, Gabriele
abstract

: Background: Kidney transplant (KT) recipients with COVID-19 are at high risk of poor outcomes due to the high burden of comorbidities and immunosuppression. The effects of immunosuppressive therapy (IST) reduction are unclear in patients with COVID-19. Methods: A retrospective study on 45 KT recipients followed at the University Hospital of Modena (Italy) who tested positive for COVID-19 by RT-PCR analysis. Results: The median age was 56.1 years (interquartile range,[IQR] 47.3-61.1), with a predominance of males (64.4%). Kidney transplantation vintage was 10.1 (2.7-16) years, and 55.6 % of patients were on triple IST before COVID-19. Early immunosuppression minimization occurred in 27 (60%) patients (reduced-dose IST group) and included antimetabolite (88.8%) and calcineurin inhibitor withdrawal (22.2%). After SARS-CoV-2 infection, 88.9% of patients became symptomatic and 42.2% required hospitalization. One patient experienced irreversible graft failure. There were no differences in serum creatinine level and proteinuria in non-hospitalized patients before and post-COVID-19, whereas hospitalized patients experienced better kidney function after hospital discharge (P=0.019). Overall mortality was 17.8%. without differences between full- and reduced-dose IST. Risk factors for death were age (odds ratio [OR]: 1.19; 95%CI: 1.01-1.39), and duration of kidney transplant (OR: 1.17; 95%CI: 1.01-1.35). One KT recipient developed IgA glomerulonephritis and two ones experienced symptomatic COVID-19 after primary infection and SARS-CoV-2 mRNA vaccine, respectively. Conclusions: Despite the reduction of immunosuppression, COVID-19 affected the survival of KT recipients. Age of patients and time elapsed from kidney transplantation were independent predictors of death . Early kidney function was favorable in most survivors after COVID-19.

2021 - Incidence, risk factors and outcome of acute kidney injury (AKI) in patients with COVID-19 [Articolo su rivista]
Alfano, Gaetano; Ferrari, Annachiara; Fontana, Francesco; Mori, Giacomo; Magistroni, Riccardo; Meschiari, Marianna; Franceschini, Erica; Menozzi, Marianna; Cuomo, Gianluca; Orlando, Gabriella; Santoro, Antonella; Digaetano, Margherita; Puzzolante, Cinzia; Carli, Federica; Bedini, Andrea; Milic, Jovana; Coloretti, Irene; Raggi, Paolo; Mussini, Cristina; Girardis, Massimo; Cappelli, Gianni; Guaraldi, Giovanni
abstract

Background Acute kidney injury (AKI) is a severe complication of coronavirus disease-2019 (COVID-19). This study aims to evaluate incidence, risk factors and case-fatality rate of AKI in patients with COVID-19. Methods We reviewed the health medical records of 307 consecutive patients with COVID-19 hospitalized at the University Hospital of Modena, Italy. Results AKI was diagnosed in 69 out of 307 (22.4%) COVID-19 patients. Stages 1, 2, or 3 AKI accounted for 57.9%, 24.6% and 17.3%, respectively. AKI patients had a mean age of 74.7 +/- 9.9 years. These patients showed higher serum levels of the main markers of inflammation and higher rate of severe pneumonia than non-AKI patients. Kidney injury was associated with a higher rate of urinary abnormalities including proteinuria (0.44 +/- 0.85 vs 0.18 +/- 0.29 mg/mg; P = < 0.0001) and microscopic hematuria (P = 0.032) compared to non-AKI patients. Hemodialysis was performed in 7.2% of the subjects and 33.3% of the survivors did not recover kidney function after AKI. Risk factors for kidney injury were age, male sex, CKD and higher non-renal SOFA score. Patients with AKI had a mortality rate of 56.5%. Adjusted Cox regression analysis revealed that COVID-19-associated AKI was independently associated with in-hospital death (hazard ratio [HR] = 4.82; CI 95%, 1.36-17.08) compared to non-AKI patients. Conclusion AKI was a common and harmful consequence of COVID-19. It manifested with urinary abnormalities (proteinuria, microscopic hematuria) and conferred an increased risk for death. Given the well-known short-term sequelae of AKI, prevention of kidney injury is imperative in this vulnerable cohort of patients.

2021 - Liver transplantation for hcc in hiv‐infected patients: Long‐term single‐center experience [Articolo su rivista]
Guerrini, G. P.; Berretta, M.; Guaraldi, G.; Magistri, P.; Esposito, G.; Ballarin, R.; Serra, V.; Di Sandro, S.; Di Benedetto, F.
abstract

Background: HIV‐infected patients now have long life expectation since the introduction of the highly active antiretroviral therapy (HAART). Liver diseases, especially cirrhosis and hepatocellular carcinoma (HCC), currently represent a leading cause of death in this setting of patients. Aim: To address the results of liver transplantation (LT) for HCC in HIV‐infected patients. Methods: All patients with and without HIV infection who underwent LT for HCC (n = 420) between 2001 and 2021 in our center were analyzed with the intent of comparing graft and patient survival. Cox regression analysis was used to determine prognostic survival factors and logistic regression to determine the predictor factors of post‐LT recurrence. Results: Among 1010 LT, 32 were HIV‐infected recipients. With an average follow‐up of 62 ± 51 months, 5‐year overall survival in LT recipients with and without HIV‐infection was 71.6% and 69.9%, respectively (p = ns), whereas 5‐year graft survival in HIV‐infected and HIV‐non infected was 68.3% and 68.2%, respectively (p = ns). The independent predictive factor of survival in the study group was: HCV infection (HR 1.83 p = 0.024). There were no significant differences in the pathological characteristics of HCC between the two groups. The logistic regression analysis of the study population demonstrated that microvascular invasion (HR 5.18 p< 0.001), HCC diameter (HR 1.16 p = 0.028), and number of HCC nodules (HR 1.26 p = 0.003) were predictors of recurrence post‐LT. Conclusion: Our study shows that HIV patients undergoing LT for HCC have comparable results in terms of post‐LT survival. Excellent results can be achieved for HIV-infected patients with HCC, as long as a strategy of close surveillance and precise treatment of the tumor is adopted while on the waiting list.

2021 - Lopinavir/Ritonavir and Darunavir/Cobicistat in Hospitalized COVID-19 Patients: Findings From the Multicenter Italian CORIST Study [Articolo su rivista]
Di Castelnuovo, Augusto; Costanzo, Simona; Antinori, Andrea; Berselli, Nausicaa; Blandi, Lorenzo; Bonaccio, Marialaura; Bruno, Raffaele; Cauda, Roberto; Gialluisi, Alessandro; Guaraldi, Giovanni; Menicanti, Lorenzo; Mennuni, Marco; My, Ilaria; Parruti, Agostino; Patti, Giuseppe; Perlini, Stefano; Santilli, Francesca; Signorelli, Carlo; Stefanini, Giulio G; Vergori, Alessandra; Ageno, Walter; Aiello, Luca; Agostoni, Piergiuseppe; Al Moghazi, Samir; Arboretti, Rosa; Aucella, Filippo; Barbieri, Greta; Barchitta, Martina; Bartoloni, Alessandro; Bologna, Carolina; Bonfanti, Paolo; Caiano, Lucia; Carrozzi, Laura; Cascio, Antonio; Castiglione, Giacomo; Chiarito, Mauro; Ciccullo, Arturo; Cingolani, Antonella; Cipollone, Francesco; Colomba, Claudia; Colombo, Crizia; Crosta, Francesco; Dalena, Giovanni; Dal Pra, Chiara; Danzi, Gian Battista; D'Ardes, Damiano; de Gaetano Donati, Katleen; Di Gennaro, Francesco; Di Tano, Giuseppe; D'Offizi, Gianpiero; Filippini, Tommaso; Maria Fusco, Francesco; Gaudiosi, Carlo; Gentile, Ivan; Gini, Giancarlo; Grandone, Elvira; Guarnieri, Gabriella; Lamanna, Gennaro L F; Larizza, Giovanni; Leone, Armando; Lio, Veronica; Losito, Angela Raffaella; Maccagni, Gloria; Maitan, Stefano; Mancarella, Sandro; Manuele, Rosa; Mapelli, Massimo; Maragna, Riccardo; Marra, Lorenzo; Maresca, Giulio; Marotta, Claudia; Mastroianni, Franco; Mazzitelli, Maria; Mengozzi, Alessandro; Menichetti, Francesco; Milic, Jovana; Minutolo, Filippo; Molena, Beatrice; Mussinelli, R; Mussini, Cristina; Musso, Maria; Odone, Anna; Olivieri, Marco; Pasi, Emanuela; Perroni, Annalisa; Petri, Francesco; Pinchera, Biagio; Pivato, Carlo A; Poletti, Venerino; Ravaglia, Claudia; Rossato, Marco; Rossi, Marianna; Sabena, Anna; Salinaro, Francesco; Sangiovanni, Vincenzo; Sanrocco, Carlo; Scorzolini, Laura; Sgariglia, Raffaella; Simeone, Paola Giustina; Spinicci, Michele; Trecarichi, Enrico Maria; Veronesi, Giovanni; Vettor, Roberto; Vianello, Andrea; Vinceti, Marco; Visconti, Elena; Vocciante, Laura; De Caterina, Raffaele; Iacoviello, Licia
abstract

Background: Protease inhibitors have been considered as possible therapeutic agents for COVID-19 patients. Objectives: To describe the association between lopinavir/ritonavir (LPV/r) or darunavir/cobicistat (DRV/c) use and in-hospital mortality in COVID-19 patients. Study Design: Multicenter observational study of COVID-19 patients admitted in 33 Italian hospitals. Medications, preexisting conditions, clinical measures, and outcomes were extracted from medical records. Patients were retrospectively divided in three groups, according to use of LPV/r, DRV/c or none of them. Primary outcome in a time-to event analysis was death. We used Cox proportional-hazards models with inverse probability of treatment weighting by multinomial propensity scores. Results: Out of 3,451 patients, 33.3% LPV/r and 13.9% received DRV/c. Patients receiving LPV/r or DRV/c were more likely younger, men, had higher C-reactive protein levels while less likely had hypertension, cardiovascular, pulmonary or kidney disease. After adjustment for propensity scores, LPV/r use was not associated with mortality (HR = 0.94, 95% CI 0.78 to 1.13), whereas treatment with DRV/c was associated with a higher death risk (HR = 1.89, 1.53 to 2.34, E-value = 2.43). This increased risk was more marked in women, in elderly, in patients with higher severity of COVID-19 and in patients receiving other COVID-19 drugs. Conclusions: In a large cohort of Italian patients hospitalized for COVID-19 in a real-life setting, the use of LPV/r treatment did not change death rate, while DRV/c was associated with increased mortality. Within the limits of an observational study, these data do not support the use of LPV/r or DRV/c in COVID-19 patients.

2021 - Methicillin-Resistant Staphylococcus aureus Peritonitis due to Hematogenous Dissemination from Central Venous Catheter in a Maintenance Dialysis Patient [Articolo su rivista]
Alfano, G.; Frisina, M.; Morisi, N.; Ascione, E.; Fontana, F.; Mori, G.; Cerami, C.; Serra, F.; Cabry, F.; Bonucchi, D.; Gelmini, R.; Guaraldi, G.; Magistroni, R.; Cappelli, G.
abstract

Staphylococcus aureus is a Gram-positive bacterium commonly associated with severe infections in hospitalized patients. S. aureus produces many virulence factors leading to local and distant pathological processes. Invasiveness of S. aureus generally induces metastatic infections such as bacteremia, infective endocarditis, osteomyelitis, arthritis, and endophthalmitis. Peritoneal localization from extra-abdominal infection can be a potential consequence of S. aureus infection. Two cases of metastatic peritonitis have been described in patients on peritoneal dialysis with concomitant peripheral vascular catheter-related bloodstream infection. We reported a case of peritoneal metastatic infection caused by methicillin-resistant Staphylococcus aureus (MRSA) in a patient on maintenance hemodialysis. A 37-year-old man was admitted with fever and chill due to jugular central vascular catheter (CVC)-related bloodstream infection caused by MRSA. CVC was placed after switching the patient from peritoneal dialysis to hemodialysis for scarce adherence to fluid restriction. Detection of MRSA on the peritoneal effluent combined with a total white blood cell count of 554 cells/mm3 prompted the diagnosis of satellite MRSA peritonitis. Antibiotic treatment with daptomycin and simultaneous CVC and peritoneal catheter removal resolved the infectious process. No further metastatic localizations were detected elsewhere. In conclusion, S. aureus can induce metastatic infections far from the site of primary infection. As reported in this case, peritonitis can be secondary to the hematogenous dissemination of S. aureus especially in hospitalized patients having a central line.

2021 - Methylprednisolone as rescue therapy after tocilizumab failure in patients with severe COVID-19 pneumonia [Articolo su rivista]
Guaraldi, Giovanni; Banchelli, Federico; Milic, Jovana; Dolci, Giovanni; Massari, Marco; Corsini, Romina; Meschiari, Marianna; Girardis, Massimo; Busani, Stefano; Cossarizza, Andrea; Salvarani, Carlo; Mussini, Cristina; D'Amico, Roberto
abstract

2021 - Monocyte Distribution Width (MDW) as novel inflammatory marker with prognostic significance in COVID-19 patients [Articolo su rivista]
Riva, G.; Castellano, S.; Nasillo, V.; Ottomano, A. M.; Bergonzini, G.; Paolini, A.; Lusenti, B.; Milic, J.; De Biasi, S.; Gibellini, L.; Cossarizza, A.; Busani, S.; Girardis, M.; Guaraldi, G.; Mussini, C.; Manfredini, R.; Luppi, M.; Tagliafico, E.; Trenti, T.
abstract

Monocyte Distribution Width (MDW), a new cytometric parameter correlating with cytomorphologic changes occurring upon massive monocyte activation, has recently emerged as promising early biomarker of sepsis. Similar to sepsis, monocyte/macrophage subsets are considered key mediators of the life-threatening hyper-inflammatory disorder characterizing severe COVID-19. In this study, we longitudinally analyzed MDW values in a cohort of 87 COVID-19 patients consecutively admitted to our hospital, showing significant correlations between MDW and common inflammatory markers, namely CRP (p < 0.001), fibrinogen (p < 0.001) and ferritin (p < 0.01). Moreover, high MDW values resulted to be prognostically associated with fatal outcome in COVID-19 patients (AUC = 0.76, 95% CI: 0.66–0.87, sensitivity 0.75, specificity 0.70, MDW threshold 26.4; RR = 4.91, 95% CI: 1.73–13.96; OR = 7.14, 95% CI: 2.06–24.71). This pilot study shows that MDW can be useful in the monitoring of COVID-19 patients, as this innovative hematologic biomarker is: (1) easy to obtain, (2) directly related to the activation state of a fundamental inflammatory cell subset (i.e. monocytes, pivotal in both cytokine storm and sepsis immunopathogenesis), (3) well correlated with clinical severity of COVID-19-associated inflammatory disorder, and, in turn, (4) endowed with relevant prognostic significance. Additional studies are needed to define further the clinical impact of MDW testing in the management of COVID-19 patients.

2021 - "Moving Fourth": Introduction of a practical toolkit for shared decision-making to facilitate healthy living beyond HIV viral suppression [Articolo su rivista]
Curran, Adrian; Arends, Joop; Buhk, Thomas; Cascio, Mario; Teofilo, Eugenio; van den Berk, Guido; Guaraldi, Giovanni
abstract

An extension of the UNAIDS 90-90-90 target proposes >90% of people living with HIV (PLHIV) should have good health-related quality of life (HrQoL); however, limited guidance exists. The "Health Goals for Me" framework, an individualized approach to HIV care, provides a framework to assess HrQoL. We analyzed several patient-reported outcome measures (PROMs) to develop a practical toolkit to facilitate shared physician-patient decision-making. HrQoL subdomains, actionable in the clinical setting and measurable as PROMs, were selected. PROMs were collated through systematic literature searches, scored by the authors on usability, validation, and availability, after which practical recommendations were made. Nine subdomains were selected across physical, psychological, social, and environmental domains; 46 validated PROMs were identified. After pre-screening, from 39 evaluated PROMs, we recommended PROMs in the following subdomains: fatigue/energy loss, frailty/resilience, sleep disturbance, substance use, anxiety/depression, cognition, sexual function and desire, and stigma. Using this toolkit, healthcare professionals and PLHIV can collaborate and mutually agree on individual care objectives. Following the "Health Goals for Me" framework, appropriate care interventions can be implemented and reviewed in a continuous cycle. We discussed how eHealth interventions, which will have increasing importance in the post-COVID era, can facilitate improved HrQoL for PLHIV by utilizing toolkits such as the one described here. Implementation of this practical framework and the PROMs toolkit could provide a useful approach to assessing HrQoL in PLHIV and could enhance the physician's ability to gain valuable insights into the patient's daily life across a broad range of HrQoL issues.

2021 - Multiple House Occupancy is Associated with Mortality in Hospitalised Patients with Covid-19 [Articolo su rivista]
Bruce, Eilidh; Carter, Ben; Quinn, Terence J; Verduri, Alessia; Pearson, Oliver; Vilches-Moraga, Arturo; Price, Angeline; Mcgovern, Aine; Evans, Louis; Mccarthy, Kathryn; Hewitt, Jonathan; Moug, Susan; Myint, Phyo K; Behalf Of Cope Study Team, Null; Einarsson, Alice; Fleck, Anna; Bisset, Carly; Alexander, Ross; Guaraldi, Giovanni; Murphy, Caroline; Kelly, Joanna; Short, Roxanna; Braude, Philip; El Jichi Mutasem, Tarik; Singh, Sandeep; Paxton, Dolcie; Harris, Will; Hesford, James; Holloway, Mark; Mitchell, Emma; Rickard, Frances; Galbraith, Norman; Bhatti, Emma; Edwards, Jenny; Duffy, Siobhan; Barlow-Pay, Fenella; Pearce, Lyndsey; Garcia, Madeline; Sangani, Shefali; Kneen, Thomas; Lee, Thomas; Davey, Charlotte; Jones, Sheila; Lunstone, Kiah; Cavenagh, Alice; Silver, Charlotte; Telford, Thomas; Simmons, Rebecca; Stechman, Michael
abstract

In response to the COVID-19 pandemic, many countries mandated staying at home to reduce transmission. This study examined the association between living arrangements (house occupancy numbers) and outcomes in COVID-19.

2021 - One-year persistence of neutralizing anti-SARS-CoV-2 antibodies in dialysis patients recovered from COVID-19 [Articolo su rivista]
Alfano, Gaetano; Fontana, Francesco; Morisi, Niccolò; Giaroni, Francesco; Mori, Giacomo; Guaraldi, Giovanni; Magistroni, Riccardo; Cappelli, Gianni; Cossarizza, Andrea; Gibellini, Lara
abstract

The immunological mechanisms that modulate immune response to SARS-CoV-2 infection remain elusive. Little is known on the magnitude and the durability of antibody response against COVID-19. There is consensus that patients with immune dysfunction, such as dialysis patients, may be unable to mount a robust and durable humoral immunity after infections. Recent studies showed that dialysis patients seroconverted after COVID-19, but data on the durability of the immune response are missing. We reported the data of a durable anti-spike protein seroconversion after natural SARS-CoV-2 infection in three patients on hemodialysis with a mean age of 67.2 +/- 13.8 years. A mean antibody titer of 212.6 +/- 174.9 UA/ml (Liaison (R), DiaSorin) was found after one year (range, 366-374 days) from the diagnosis of COVID-19. In conclusion, this case series provided evidence that patients receiving hemodialysis who recovered from severe COVID-19 were able to mount a long-lasting immune response against SARS-CoV-2. Although the protective capacity of this long-term immunity remains to be determined, these patients did not report signs of reinfection after recovery from COVID-19.

2021 - Patient-reported olfactory recovery after SARS-CoV-2 infection: A 6-month follow-up study [Articolo su rivista]
Lucidi, D.; Molinari, G.; Silvestri, M.; De Corso, E.; Guaraldi, G.; Mussini, C.; Presutti, L.; Fernandez, I. J.
abstract

2021 - Persistent SARS-CoV-2 positivity: An intriguing puzzle among reinfection, RNA remnants and genomic integration in COVID-19 [Articolo su rivista]
Ferrari, Annachiara; Alfano, Gaetano; Guaraldi, Giovanni
abstract

2021 - Prevalence and Outcomes for Heavily Treatment-Experienced Individuals Living With Human Immunodeficiency Virus in a European Cohort [Articolo su rivista]
Pelchen-Matthews, A.; Borges, A. H.; Reekie, J.; Rasmussen, L. D.; Wiese, L.; Weber, J.; Pradier, C.; Degen, O.; Paredes, R.; Tau, L.; Flamholc, L.; Gottfredsson, M.; Kowalska, J. D.; Jablonowska, E.; Mozer-Lisewska, I.; Radoi, R.; Vasylyev, M.; Kuznetsova, A.; Begovac, J.; Svedhem, V.; Clark, A.; Cozzi-Lepri, A.; Harxhi, A.; Losso, M.; Kundro, M.; Schmied, B.; Zangerle, R.; Karpov, I.; Vassilenko, A.; Mitsura, V. M.; Paduto, D.; Clumeck, N.; De Wit, S.; Delforge, M.; Florence, E.; Vandekerckhove, L.; Hadziosmanovic, V.; Machala, L.; Jilich, D.; Sedlacek, D.; Kronborg, G.; Benfield, T.; Gerstoft, J.; Katzenstein, T.; Pedersen, C.; Johansen, I. S.; Ostergaard, L.; Moller, N. F.; Nielsen, L. N.; Zilmer, K.; Smidt, J.; Aho, I.; Viard, J. -P.; Girard, P. -M.; Fontas, E.; Duvivier, C.; Rockstroh, J.; Behrens, G.; Stellbrink, H. J.; Stephan, C.; Goethe, J. W.; Bogner, J.; Fatkenheuer, G.; Chkhartishvili, N.; Sambatakou, H.; Adamis, G.; Paissios, N.; Szlavik, J.; Kelly, C.; Turner, D.; Burke, M.; Shahar, E.; Hassoun, G.; Elinav, H.; Haouzi, M.; Elbirt, D.; D'Arminio Monforte, A.; Esposito, R.; Mazeu, I.; Mussini, C.; Mazzotta, F.; Gabbuti, A.; Lazzarin, A.; Castagna, A.; Gianotti, N.; Galli, M.; Ridolfo, A.; Uzdaviniene, V.; Matulionyte, R.; Staub, T.; Hemmer, R.; Dragas, S.; Stevanovic, M.; Reiss, P.; Trajanovska, J.; Reikvam, D. H.; Maeland, A.; Bruun, J.; Knysz, B.; Gasiorowski, J.; Inglot, M.; Bakowska, E.; Flisiak, R.; Grzeszczuk, A.; Parczewski, M.; Maciejewska, K.; Aksak-Was, B.; Beniowski, M.; Mularska, E.; Kamerys, J.; Wojcik, K.; Rozplochowski, B.; Zagalo, A.; Mansinho, K.; Maltez, F.; Oprea, C.; Yakovlev, A.; Trofimora, T.; Khromova, I.; Kuzovatova, E.; Borodulina, E.; Vdoushkina, E.; Ranin, J.; Tomazic, J.; Miro, J. M.; Miro, J. M.; Laguno, M.; Martinez, E.; Garcia, F.; Blanco, J. L.; Martinez-Rebollar, M.; Mallolas, J.; Callau, P.; Rojas, J.; Inciarta, A.; Moreno, S.; del Campo, S.; Clotet, B.; Jou, A.; Puig, J.; Llibre, J. M.; Santos, J. R.; Domingo, P.; Gutierrez, M.; Mateo, G.; Sambeat, M. A.; Laporte, J. M.; Falconer, K.; Thalme, A.; Sonnerborg, A.; Treutiger, C. J.; Scherrer, A.; Weber, R.; Cavassini, M.; Calmy, A.; Furrer, H.; Battegay, M.; Schmid, P.; Mikhalik, J.; Sluzhynska, M.; Milinkovic, A.; Johnson, A. M.; Simons, E.; Edwards, S.; Phillips, A.; Johnson, M. A.; Mocroft, A.; Orkin, C.; Winston, A.; Leen, C.; Wandeler, G.; Lundgren, J.; Guaraldi, G.; Kirk, O.; Peters, L.; Bojesen, A.; Raben, D.; Hansen, E. V.; Kristensen, D.; Larsen, J. F.; Fischer, A. H.; Amele, S.; Roen, A.
abstract

Background: Although antiretroviral treatments have improved survival of persons living with HIV, their long-term use may limit available drug options. We estimated the prevalence of heavily treatmentexperienced (HTE) status and the potential clinical consequences of becoming HTE. Setting: EuroSIDA, a European multicenter prospective cohort study. Methods: A composite definition for HTE was developed, based on estimates of antiretroviral resistance and prior exposure to specific antiretroviral regimens. Risks of progressing to clinical outcomes were assessed by Poisson regression, comparing every HTE individual with 3 randomly selected controls who never became HTE. Results: Of 15,570 individuals under follow-up in 2010-2016, 1617 (10.4%, 95% CI: 9.9% to 10.9%) were classified as HTE. 1093 individuals became HTE during prospective follow-up (HTE incidence rate 1.76, CI: 1.66 to 1.87 per 100 person-years of follow-up). The number of HTE individuals was highest in West/Central Europe (636/4019 persons, 15.7%) and lowest in East Europe (26/2279 persons, 1.1%). Although most HTE individuals maintained controlled viral loads (<400 copies/mL), many had low CD4 counts (≤350 cells/μL). After controlling for age, immunological parameters and pre-existing comorbidities, HTE status was not associated with the risk of new AIDS (adjusted incidence rate ratio, aIRR 1.44, CI: 0.86 to 2.40, P = 0.16) or non-AIDS clinical events (aIRR 0.96, CI: 0.74 to 1.25, P = 0.77). Conclusions: HTE prevalence increased with time. After adjusting for key confounding factors, there was no evidence for an increased risk of new AIDS or non-AIDS clinical events in HTE. Additional therapeutic options and effective management of comorbidities remain important to reduce clinical complications in HTE individuals.

2021 - Re: 'methodological evaluation of bias in observational COVID-19 studies on drug effectiveness' by Wolkewitz et al [Articolo su rivista]
Cozzi-Lepri, Alessandro; Guaraldi, Giovanni; Meschiari, Marianna; Mussini, Cristina
abstract

2021 - Re: “No Significant Changes in Weight and Body Fat Mass in Suppressed HIV Infected Patients Switched to Dual Combination Lamivudine Plus Dolutegravir or Raltegravir” by Calza et al. [Articolo su rivista]
Ciccullo, Arturo; Baldin, Gianmaria; Borghi, Vanni; Lassandro, Anna Pia; Farinacci, Damiano; Guaraldi, Giovanni; Mussini, Cristina; Di Giambenedetto, Simona
abstract

N/A.

2021 - Risk for non-AIDS-defining and AIDS-defining cancer of early versus delayed initiation of antiretroviral therapy: A multinational prospective cohort study [Articolo su rivista]
Chammartin, F.; Lodi, S.; Logan, R.; Ryom, L.; Mocroft, A.; Kirk, O.; D'Arminio Monforte, A.; Reiss, P.; Phillips, A.; El-Sadr, W.; Hatleberg, C. I.; Pradier, C.; Bonnet, F.; Law, M.; De Wit, S.; Sabin, C.; Lundgren, J. D.; Bucher, H. C.; Calvo, G.; Dabis, F.; Morfeldt, L.; Weber, R.; Lind-Thomsen, A.; Salbol Brandt, R.; Hillebreght, M.; Zaheri, S.; Wit, F. W. N. M.; Scherrer, A.; Schoni-Affolter, F.; Rickenbach, M.; Tavelli, A.; Fanti, I.; Leleux, O.; Mourali, J.; Le Marec, F.; Boerg, E.; Thulin, E.; Sundstrom, A.; Bartsch, G.; Thompsen, G.; Necsoi, C.; Delforge, M.; Fontas, E.; Caissotti, C.; Dollet, K.; Mateu, S.; Torres, F.; Petoumenos, K.; Blance, A.; Huang, R.; Puhr, R.; Gronborg Laut, K.; Kristensen, D.; Kamara, D. A.; Smith, C. J.; Raben, D.; Matthews, C.; Bojesen, A.; Grevsen, A. L.; Powderly, B.; Shortman, N.; Moecklinghoff, C.; Reilly, G.; Smit, C.; Ross, M.; Fux, C. A.; Morlat, P.; Friis-Moller, N.; Kowalska, J.; Bohlius, J.; Bower, M.; Fatkenheuer, G.; Grulich, A.; Sjol, A.; Meidahl, P.; Iversen, J. S.; Hillebregt, M.; Prins, J. M.; Kuijpers, T. W.; Scherpbier, H. J.; Van Der Meer, J. T. M.; Godfried, M. H.; Van Der Poll, T.; Nellen, F. J. B.; Geerlings, S. E.; Van Vugt, M.; Pajkrt, D.; Bos, J. C.; Wiersinga, W. J.; Van Der Valk, M.; Goorhuis, A.; Hovius, J. W.; Van Eden, J.; Henderiks, A.; Van Hes, A. M. H.; Mutschelknauss, M.; Nobel, H. E.; Pijnappel, F. J. J.; Jurriaans, S.; Back, N. K. T.; Zaaijer, H. L.; Berkhout, B.; Cornelissen, M. T. E.; Schinkel, C. J.; Thomas, X. V.; Van Den Berge, M.; Stegeman, A.; Baas, S.; Hage De Looff, L.; Versteeg, D.; Pronk, M. J. H.; Ammerlaan, H. S. M.; de Munnik, E. S.; Jansz, A. R.; Tjhie, J.; Wegdam, M. C. A.; Deiman, B.; Scharnhorst, V.; Van Der Plas, A.; Weijsenfeld, A. M.; Van Der Ende, M. E.; de Vries-Sluijs, T. E. M. S.; van Gorp, E. C. M.; Schurink, C. A. M.; Nouwen, J. L.; Verbon, A.; Rijnders, B. J. A.; Bax, H. I.; Van Der Feltz, M.; Bassant, N.; Van Beek, J. E. A.; Vriesde, M.; Van Zonneveld, L. M.; De Oude-Lubbers, A.; Van Den Berg-Cameron, H. J.; Bruinsma-Broekman, F. B.; de Groot, J.; De Zeeuw-De Man, M.; Boucher, C. A. B.; Koopmans, M. P. G.; van Kampen, J. J. A.; Pas, S. D.; Driessen, G. J. A.; van Rossum, A. M. C.; Van Der Knaap, L. C.; Visser, E.; Branger, J.; Rijkeboer-Mes, A.; Duijf-Van De Ven, C. J. H. M.; Schippers, E. F.; van Nieuwkoop, C.; van IJperen, J. M.; Geilings, J.; van der Hut, G.; Franck, P. F. H.; Van Eeden, A.; Brokking, W.; Groot, M.; Elsenburg, L. J. M.; Damen, M.; Kwa, I. S.; Groeneveld, P. H. P.; Bouwhuis, J. W.; Van Den Berg, J. F.; Van Hulzen, A. G. W.; Van Der Bliek, G. L.; Bor, P. C. J.; Bloembergen, P.; Wolfhagen, M. J. H. M.; Ruijs, G. J. H. M.; Kroon, F. P.; De Boer, M. G. J.; Bauer, M. P.; Jolink, H.; Vollaard, A. M.; Dorama, W.; Van Holten, N.; Claas, E. C. J.; Wessels, E.; Den Hollander, J. G.; Pogany, K.; Roukens, A.; Kastelijns, M.; Smit, J. V.; Smit, E.; Struik-Kalkman, D.; Tearno, C.; Bezemer, M.; van Niekerk, T.; Pontesilli, O.; Lowe, S. H.; Oude Lashof, A. M. L.; Posthouwer, D.; Ackens, R. P.; Schippers, J.; Vergoossen, R.; Weijenberg-Maes, B.; van Loo, I. H. M.; Havenith, T. R. A.; Leyten, E. M. S.; Gelinck, L. B. S.; van Hartingsveld, A.; Meerkerk, C.; Wildenbeest, G. S.; Mutsaers, J. A. E. M.; Jansen, C. L.; Mulder, J. W.; Vrouenraets, S. M. E.; Lauw, F. N.; van Broekhuizen, M. C.; Paap, H.; Vlasblom, D. J.; Smits, P. H. M.; Weijer, S.; El Moussaoui, R.; Bosma, A. S.; van Vonderen, M. G. A.; van Houte, D. P. F.; Kampschreur, L. M.; Dijkstra, K.; Faber, S.; Weel, J.; Kootstra, G. J.; Delsing, C. E.; van der Burg-Van de Plas, M.; Heins, H.; Lucas, E.; Kortmann, W.; van Twillert, G.; Cohen Stuart, J. W. T.; Diederen, B. M. W.; van Truijen-Oud, F. A.; van der Reijden, W. A.; Jansen, R.; Brinkman, K.; van den Berk, G. E. L.; Blok, W. L.; Frissen, P. H. J.; Lettinga, K. D.; Schouten, W. E. M.; Veenstra, J.; Brouwer, J. C.; Geerders, F. G.; Hoeksema, K.; Kleene, J. M.; van der Meche, B. I.; Spelbrink, M.; Sulman, H.; Toonen, A.
abstract

Background: Immediate initiation of antiretroviral therapy (ART) regardless of CD4 cell count reduces risk for AIDS and non-AIDS-related events in asymptomatic, HIV-positive persons and is the standard of care. However, most HIV-positive persons initiate ART when their CD4 count decreases below 500 × 109 cells/L. Consequences of delayed ART on risk for non-AIDS-defining and AIDS-defining cancer, one of the most common reasons for death in HIV, are unclear. Objective: To estimate the long-term risk difference for cancer with the immediate ART strategy. Design: Multinational prospective cohort study. Setting: The D:A:D (Data collection on Adverse events of anti-HIV Drugs) study, which included HIV-positive persons from Europe, Australia, and the United States. Participants: 8318 HIV-positive persons with at least 1 measurement each of CD4 cell count and viral load while ART-naive (study period, 2006 to 2016). Measurements: The parametric g-formula was used, with adjustment for baseline and time-dependent confounders (CD4 cell count and viral load), to assess the 10-year risk for non-AIDS-defining and AIDS-defining cancer of immediate versus deferred (at CD4 counts < 350 and < 500 × 109 cells/L) ART initiation strategies. Results: During 64 021 person-years of follow-up, 231 cases of non-AIDS-defining cancer and 272 of AIDS-defining cancer occurred among HIV-positive persons with a median age of 36 years (interquartile range, 29 to 43 years). With immediate ART, the 10-year risk for non-AIDS-defining cancer was 2.97% (95% CI, 2.37% to 3.50%) and that for AIDS-defining cancer was 2.50% (CI, 2.37% to 3.38%). Compared with immediate ART initiation, the 10-year absolute risk differences when deferring ART to CD4 counts less than 500 × 109 cells/L and less than 350 × 109 cells/L were 0.12 percentage point (CI, -0.01 to 0.26 percentage point) and 0.29 percentage point (CI, -0.03 to 0.73 percentage point), respectively, for non-AIDS-defining cancer and 0.32 percentage point (CI, 0.21 to 0.44 percentage point) and 1.00 percentage point (CI, 0.67 to 1.44 percentage points), respectively, for AIDS-defining cancer. Limitation: Potential residual confounding due to observational study design. Conclusion: In this young cohort, effects of immediate ART on 10-year risk for cancer were small, and further supportive data are needed for non-AIDS-defining cancer. Primary Funding Source: Highly Active Antiretroviral Therapy Oversight Committee.

2021 - Sarcopenic obesity at the crossroad of pathogenesis of cardiometabolic diseases [Articolo su rivista]
Guaraldi, G.; Milic, J.; Sebastiani, G.; Raggi, P.
abstract

2021 - Sarilumab in patients admitted to hospital with severe or critical COVID-19: a randomised, double-blind, placebo-controlled, phase 3 trial [Articolo su rivista]
Lescure, F. -X.; Honda, H.; Fowler, R. A.; Lazar, J. S.; Shi, G.; Wung, P.; Patel, N.; Hagino, O.; Bazzalo, I. J.; Casas, M. M.; Nunez, S. A.; Pere, Y.; Ibarrola, C. M.; Solis Aramayo, M. A.; Cuesta, M. C.; Duarte, A. E.; Gutierrez Fernandez, P. M.; Iannantuono, M. A.; Miyazaki, E. A.; Silvio, J. P.; Scublinsky, D. G.; Bales, A.; Catarino, D.; Fiss, E.; Mohrbacher, S.; Sato, V.; Baylao, A.; Cavalcante, A.; Correa, F.; de Andrade, C. A.; Furtado, J.; Ribeiro Filho, N.; Telles, V.; Trevelin, L. T.; Vipich, R.; Boldo, R.; Borges, P.; Lobo, S.; Luckemeyer, G.; Machado, L.; Alves, M. B.; Iglessias, A. C.; Lago, M. M.; Santos, D. W.; Chapdelaine, H.; Falcone, E. L.; Jamal, R.; Luong, M. -L.; Durand, M.; Doucet, S.; Carrier, F. -M.; Coburn, B. A.; Del Sorbo, L.; Walmsley, S. L.; Belga, S.; Chen, L. Y.; Mah, A. D.; Steiner, T.; Wright, A. J.; Hajek, J.; Adhikari, N.; Fowler, R. A.; Daneman, N.; Khwaja, K. A.; Shahin, J.; Gonzalez, C.; Silva, R.; Lindh, M.; Maluenda, G.; Fernandez, P.; Oyonarte, M.; Lasso, M.; Boyer, A.; Bronnimann, D.; Bui, H. -N.; Cazanave, C.; Chaussade, H.; Desclaux, A.; Ducours, M.; Duvignaud, A.; Malvy, D.; Martin, L.; Neau, D.; Nguyen, D.; Pistone, T.; Soubrane-Wirth, G.; Leitao, J.; Allavena, C.; Biron, C.; Bouchez, S.; Gaborit, B.; Gregoire, A.; Le Turnier, P.; Lecompte, A. -S.; Lecomte, R.; Lefebvre, M.; Raffi, F.; Boutoille, D.; Morineau, P. H.; Guery, R.; Chatelus, E.; Dumoussaud, N.; Felten, R.; Luca, F.; Goichot, B.; Schneider, F.; Taquet, M. -C.; Groh, M.; Roumier, M.; Neuville, M.; Bachelard, A.; Isernia, V.; Lescure, F. -X.; Phung, B. -C.; Rachline, A.; Sautereau, A.; Vallois, D.; Bleher, Y.; Boucher, D.; Coudon, C.; Esnault, J.; Guimard, T.; Leautez-Nainville, S.; Merrien, D.; Morrier, M.; Motte-Vincent, P.; Gabeff, R.; Leclerc, H.; Cozic, C.; Decours, R.; Fevrier, R.; Colin, G.; Abgrall, S.; Vignes, D.; Sterpu, R.; Kuellmar, M.; Meersch-Dini, M.; Weiss, R.; Zarbock, A.; Antony, C.; Berger, M.; Brenner, T.; Taube, C.; Herbstreit, F.; Dolff, S.; Konik, M.; Schmidt, K.; Zettler, M.; Witzke, O.; Boell, B.; Garcia Borrega, J.; Koehler, P.; Zander, T.; Dusse, F.; Al-Sawaf, O.; Kohler, P.; Eichenauer, D.; Kochanek, M.; Shimabukuro-Vornhagen, A.; Mellinghoff, S.; Classen, A.; Heger, J. -M.; Meyer-Schwickerath, C.; Liedgens, P.; Heindel, K.; Belkin, A.; Biber, A.; Gilboa, M.; Levy, I.; Litachevsky, V.; Rahav, G.; Finesod Wiedner, A.; Zilberman-Daniels, T.; Oster, Y.; Strahilevitz, J.; Sviri, S.; Baldissera, E. M.; Campochiaro, C.; Cavalli, G.; Dagna, L.; De Luca, G.; Della Torre, E.; Tomelleri, A.; Bernasconi De Luca, D.; Capetti, A. F.; Coen, M.; Cossu, M. V.; Galli, M.; Giacomelli, A.; Gubertini, G. A.; Rusconi, S.; Burastero, G. J.; Digaetano, M.; Guaraldi, G.; Meschiari, M.; Mussini, C.; Puzzolante, C.; Volpi, S.; Aiello, M.; Ariani, A.; Chetta, A. A.; Frizzelli, A.; Ticinesi, A.; Tuttolomondo, D.; Aliberti, S.; Blasi, F. B.; Di Pasquale, M. F.; Misuraca, S.; Pilocane, T.; Simonetta, E.; Aghelmo, A. M.; Angelini, C.; Brunetta, E.; Canonica, G. W.; Ciccarelli, M.; Dal Farra, S.; De Santis, M.; Ferri, S.; Folci, M.; Guidelli, G. M.; Heffler, E. M.; Loiacono, F.; Malipiero, G.; Paoletti, G.; Pedale, R.; Puggioni, F. A.; Racca, F.; Zumbo, A.; Satou, M.; Lisun, T.; Protsenko, D.; Rubtsov, N.; Beloglazova, I.; Fomina, D.; Lysenko, M.; Serdotetskova, S.; Firstov, V.; Gordeev, I.; Kokorin, I.; Komissarova, K.; Lapochkina, N.; Luchinkina, E.; Malimon, V.; Mamedguseyinova, S.; Polubatonova, K.; Suvorova, N.; Arribas, J.; Borobia Perez, A. M.; de la Calle Prieto, F.; Figueira, J. C.; Motejano Sanchez, R.; Mora-Rillo, M.; Prados Sanchez, C.; Queiruga Parada, J.; Fernandez Arnalich, F.; Guerro Barrientos, M.; Bendala Estrada, A.; Caballero Marcos, A.; Garcia Leoni, M. E.; Garcia-Martinez, R.; Collado, A. M.; Munoz Garcia, P.; Torres do Rego, A.; Villalba Garcia, M. V.; Burrillo, A.; Valerio Minero, M.; Gijon Vidaurreta, P.; Infante Herrero, S.; Velilla, E.; Machado, M.; Olmedo, M.; Pinilla, B.; Almirante Gragera, B.;
abstract

Background: Elevated proinflammatory cytokines are associated with greater COVID-19 severity. We aimed to assess safety and efficacy of sarilumab, an interleukin-6 receptor inhibitor, in patients with severe (requiring supplemental oxygen by nasal cannula or face mask) or critical (requiring greater supplemental oxygen, mechanical ventilation, or extracorporeal support) COVID-19. Methods: We did a 60-day, randomised, double-blind, placebo-controlled, multinational phase 3 trial at 45 hospitals in Argentina, Brazil, Canada, Chile, France, Germany, Israel, Italy, Japan, Russia, and Spain. We included adults (≥18 years) admitted to hospital with laboratory-confirmed SARS-CoV-2 infection and pneumonia, who required oxygen supplementation or intensive care. Patients were randomly assigned (2:2:1 with permuted blocks of five) to receive intravenous sarilumab 400 mg, sarilumab 200 mg, or placebo. Patients, care providers, outcome assessors, and investigators remained masked to assigned intervention throughout the course of the study. The primary endpoint was time to clinical improvement of two or more points (seven point scale ranging from 1 [death] to 7 [discharged from hospital]) in the modified intention-to-treat population. The key secondary endpoint was proportion of patients alive at day 29. Safety outcomes included adverse events and laboratory assessments. This study is registered with ClinicalTrials.gov, NCT04327388; EudraCT, 2020-001162-12; and WHO, U1111-1249-6021. Findings: Between March 28 and July 3, 2020, of 431 patients who were screened, 420 patients were randomly assigned and 416 received placebo (n=84 [20%]), sarilumab 200 mg (n=159 [38%]), or sarilumab 400 mg (n=173 [42%]). At day 29, no significant differences were seen in median time to an improvement of two or more points between placebo (12·0 days [95% CI 9·0 to 15·0]) and sarilumab 200 mg (10·0 days [9·0 to 12·0]; hazard ratio [HR] 1·03 [95% CI 0·75 to 1·40]; log-rank p=0·96) or sarilumab 400 mg (10·0 days [9·0 to 13·0]; HR 1·14 [95% CI 0·84 to 1·54]; log-rank p=0·34), or in proportions of patients alive (77 [92%] of 84 patients in the placebo group; 143 [90%] of 159 patients in the sarilumab 200 mg group; difference −1·7 [−9·3 to 5·8]; p=0·63 vs placebo; and 159 [92%] of 173 patients in the sarilumab 400 mg group; difference 0·2 [−6·9 to 7·4]; p=0·85 vs placebo). At day 29, there were numerical, non-significant survival differences between sarilumab 400 mg (88%) and placebo (79%; difference +8·9% [95% CI −7·7 to 25·5]; p=0·25) for patients who had critical disease. No unexpected safety signals were seen. The rates of treatment-emergent adverse events were 65% (55 of 84) in the placebo group, 65% (103 of 159) in the sarilumab 200 mg group, and 70% (121 of 173) in the sarilumab 400 mg group, and of those leading to death 11% (nine of 84) were in the placebo group, 11% (17 of 159) were in the sarilumab 200 mg group, and 10% (18 of 173) were in the sarilumab 400 mg group. Interpretation: This trial did not show efficacy of sarilumab in patients admitted to hospital with COVID-19 and receiving supplemental oxygen. Adequately powered trials of targeted immunomodulatory therapies assessing survival as a primary endpoint are suggested in patients with critical COVID-19. Funding: Sanofi and Regeneron Pharmaceuticals.

2021 - Seroconversion after COVID-19 vaccine in a dialysis patient on immunosuppressants [Articolo su rivista]
Alfano, Gaetano; Fontana, Francesco; Mori, Giacomo; Giovanella, Silvia; Giaroni, Francesco; Ligabue, Giulia; Guaraldi, Giovanni; Magistroni, Riccardo; Cappelli, Gianni
abstract

2021 - Switching from boosted PIs to dolutegravir decreases soluble CD14 and adiponectin in high cardiovascular risk people living with HIV [Articolo su rivista]
González-Cordón, Ana; Assoumou, Lambert; Moyle, Graeme; Waters, Laura; Johnson, Margaret; Domingo, Pere; Fox, Julie; Stellbrink, Hans-Jürgen; Guaraldi, Giovanni; Masiá, Mar; Gompels, Mark; De Wit, Stephane; Florence, Eric; Esser, Stefan; Raffi, François; Behrens, Georg; Pozniak, Anton; Gatell, José M; Martínez, Esteban
abstract

Switching from boosted PIs to dolutegravir in people living with HIV (PLWH) with high cardiovascular risk improved plasma lipids at 48 weeks in the NEAT022 trial. Whether this strategy may have an impact on cardiovascular biomarkers is unknown.

2021 - The association between hepatitis B virus infection and nonliver malignancies in persons living with HIV: results from the EuroSIDA study [Articolo su rivista]
Mocroft, A.; Miro, J. M.; Wandeler, G.; Llibre, J. M.; Boyd, A.; van Bremen, K.; Beniowski, M.; Mikhalik, J.; Cavassini, M.; Maltez, F.; Duvivier, C.; Uberti Foppa, C.; Knysz, B.; Bakowska, E.; Kuzovatova, E.; Domingo, P.; Zagalo, A.; Viard, J. -P.; Degen, O.; Milinkovic, A.; Benfield, T.; Peters, L.; Harxhi, A.; Losso, M.; Kundro, M.; Schmied, B.; Zangerle, R.; Karpov, I.; Vassilenko, A.; Mitsura, V. M.; Paduto, D.; Clumeck, N.; De Wit, S.; Delforge, M.; Florence, E.; Vandekerckhove, L.; Hadziosmanovic, V.; Begovac, J.; Machala, L.; Sedlacek, D.; Kronborg, G.; Gerstoft, J.; Katzenstein, T.; Pedersen, C.; Johansen, I. S.; Ostergaard, L.; Wiese, L.; Moller, N. F.; Nielsen, L. N.; Zilmer, K.; Smidt, J.; Aho, I.; Lacombe, K.; Pradier, C.; Fontas, E.; Rockstroh, J.; Behrens, G.; Hoffmann, C.; Stellbrink, H. J.; Stefan, C.; Bogner, J.; Fatkenheuer, G.; Chkhartishvili, N.; Sambatakou, H.; Adamis, G.; Paissios, N.; Szlavik, J.; Gottfredsson, M.; Devitt, E.; Tau, L.; Turner, D.; Burke, M.; Shahar, E.; Wattad, L. M.; Elinav, H.; Haouzi, M.; Elbirt, D.; D'Arminio Monforte, A.; Esposito, R.; Mazeu, I.; Mussini, C.; Mazzotta, F.; Gabbuti, A.; Lazzarin, A.; Castagna, A.; Gianotti, N.; Galli, M.; Ridolfo, A.; Uzdaviniene, V.; Matulionyte, R.; Staub, T.; Hemmer, R.; Dragas, S.; Stevanovic, M.; vd Valk, M.; Trajanovska, J.; Reikvam, D. H.; Maeland, A.; Bruun, J.; Szetela, B.; Inglot, M.; Flisiak, R.; Grzeszczuk, A.; Parczewski, M.; Maciejewska, K.; Aksak-Was, B.; Mularska, E.; Jablonowska, E.; Kamerys, J.; Wojcik, K.; Mozer-Lisewska, I.; Rozplochowski, B.; Mansinho, K.; Radoi, R.; Oprea, C.; Gusev, D.; Trofimova, T.; Khromova, I.; Borodulina, E.; Ranin, J.; Tomazic, J.; Miro, J. M.; Laguno, M.; Martinez, E.; Garcia, F.; Blanco, J. L.; Martinez-Rebollar, M.; Mallolas, J.; Callau, P.; Rojas, J.; Inciarta, A.; Moreno, S.; del Campo, S.; Clotet, B.; Jou, A.; Paredes, R.; Puig, J.; Santos, J. R.; Gutierrez, M.; Mateo, G.; Sambeat, M. A.; Laporte, J. M.; Svedhem, V.; Thalme, A.; Sonnerborg, A.; Brannstrom, J.; Flamholc, L.; Kusejko, K.; Braun, D.; Calmy, A.; Furrer, H.; Battegay, M.; Schmid, P.; Kuznetsova, A.; Sluzhynska, M.; Johnson, A. M.; Simons, E.; Edwards, S.; Phillips, A.; Johnson, M. A.; Orkin, C.; Winston, A.; Clarke, A.; Leen, C.; Karpov, I.; Losso, M.; Lundgren, J.; Rockstroh, J.; Aho, I.; Rasmussen, L. D.; Svedhem, V.; Pradier, C.; Chkhartishvili, N.; Matulionyte, R.; Oprea, C.; Kowalska, J. D.; Begovac, J.; Miro, J. M.; Guaraldi, G.; Paredes, R.; Paredes, R.; Larsen, J. F.; Bojesen, A.; Neesgaard, B.; Jaschinski, N.; Fursa, O.; Sather, M.; Raben, D.; Hansen, E. V.; Kristensen, D.; Fischer, A. H.; Jensen, S. K.; Elsing, T. W.; Phillips, A.; Reekie, J.; Cozzi-Lepri, A.; Amele, S.; Pelchen-Matthews, A.; Roen, A.; Tusch, E. S.; Bannister, W.
abstract

Objectives: The aim of this study was to assess the impact of hepatitis B virus (HBV) infection on non-liver malignancies in people living with HIV (PLWH). Methods: All persons aged ≥ 18 years with known hepatitis B virus (HBV) surface antigen (HBsAg) status after the latest of 1 January 2001 and enrolment in the EuroSIDA cohort (baseline) were included in the study; persons were categorized as HBV positive or negative using the latest HBsAg test and followed to their first diagnosis of nonliver malignancy or their last visit. Results: Of 17 485 PLWH included in the study, 1269 (7.2%) were HBV positive at baseline. During 151 766 person-years of follow-up (PYFU), there were 1298 nonliver malignancies, 1199 in those currently HBV negative [incidence rate (IR) 8.42/1000 PYFU; 95% confidence interval (CI) 7.94–8.90/1000 PYFU] and 99 in those HBV positive (IR 10.54/1000 PYFU; 95% CI 8.47–12.62/1000 PYFU). After adjustment for baseline confounders, there was a significantly increased incidence of nonliver malignancies in HBV-positive versus HBV-negative individuals [adjusted incidence rate ratio (aIRR) 1.23; 95% CI 1.00–1.51]. Compared to HBV-negative individuals, HBsAg-positive/HBV-DNA-positive individuals had significantly increased incidences of nonliver malignancies (aIRR 1.37; 95% CI 1.00–1.89) and NHL (aIRR 2.57; 95% CI 1.16–5.68). There was no significant association between HBV and lung or anal cancer. Conclusions: We found increased rates of nonliver malignancies in HBsAg-positive participants, the increases being most pronounced in those who were HBV DNA positive and for NHL. If confirmed, these results may have implications for increased cancer screening in HIV-positive subjects with chronic HBV infection.

2021 - The impact of chest CT body composition parameters on clinical outcomes in COVID-19 patients [Articolo su rivista]
Besutti, Giulia; Pellegrini, Massimo; Ottone, Marta; Cantini, Michele; Milic, Jovana; Bonelli, Efrem; Dolci, Giovanni; Cassone, Giulia; Ligabue, Guido; Spaggiari, Lucia; Pattacini, Pierpaolo; Fasano, Tommaso; Canovi, Simone; Massari, Marco; Salvarani, Carlo; Guaraldi, Giovanni; Rossi, Paolo Giorgi; Canovi, Simoneg; Massari, Marcoh; Salvarani, Carloi; Guaraldi, Giovannif; Rossi, Paolo Giorgie; Grilli, Roberto; Marino, Massimiliano; Formoso, Giulio; Formisano, Debora; Bedeschi, Emanuela; Perilli, Cinzia; la Rosa, Elisabetta; Bisaccia, Eufemia; Venturi, Ivano; Vicentini, Massimo; Campari, Cinzia; Gioia, Francesco; Broccoli, Serena; Iotti, Valentina; Mancuso, Pamela; Nitrosi, Andrea; Foracchia, Marco; Colla, Rossana; Zerbini, Alessandro; Ferrari, Anna Maria; Pinotti, Mirco; Facciolongo, Nicola; Lattuada, Ivana; Trabucco, Laura; de Pietri, Stefano; Danelli, Giorgio Francesco; Albertazzi, Laura; Bellesia, Enrica; Corradini, Mattia; Mag-Nani, Elena; Pilia, Annalisa; Polese, Alessandra; Incerti, Silvia Storchi; Zaldini, Piera; Bonanno, Orsola; Revelli, Matteo; Pinto, Carmine; Venturelli, Francesco; Teopompi, Elisabetta; Gallina, Annalisa; Bertellini, Annalisa; Costi, Stefania; Fugazzaro, Stefania
abstract

We assessed the impact of chest CT body composition parameters on outcomes and disease severity at hospital presentation of COVID-19 patients, focusing also on the possible mediation of body composition in the relationship between age and death in these patients. Chest CT scans performed at hospital presentation by consecutive COVID-19 patients (02/27/2020-03/13/2020) were retrospectively reviewed to obtain pectoralis muscle density and total, visceral, and intermuscular adipose tissue areas (TAT, VAT, IMAT) at the level of T7-T8 vertebrae. Primary outcomes were: hospitalization, mechanical ventilation (MV) and/or death, death alone. Secondary outcomes were: C-reactive protein (CRP), oxygen saturation (SO2), CT disease extension at hospital presentation. The mediation of body composition in the effect of age on death was explored. Of the 318 patients included in the study (median age 65.7 years, females 37.7%), 205 (64.5%) were hospitalized, 68 (21.4%) needed MV, and 58 (18.2%) died. Increased muscle density was a protective factor while increased TAT, VAT, and IMAT were risk factors for hospitalization and MV/death. All these parameters except TAT had borderline effects on death alone. All parameters were associated with SO2 and extension of lung parenchymal involvement at CT; VAT was associated with CRP. Approximately 3% of the effect of age on death was mediated by decreased muscle density. In conclusion, low muscle quality and ectopic fat accumulation were associated with COVID-19 outcomes, VAT was associated with baseline inflammation. Low muscle quality partly mediated the effect of age on mortality.

2021 - The Impact of COVID-19 on UNAIDS 90-90-90 Targets: Calls for New HIV Care Models [Articolo su rivista]
Guaraldi, G.; Borghi, V.; Milic, J.; Carli, F.; Cuomo, G.; Menozzi, M.; Santoro, A.; Orlando, G.; Puzzolante, C.; Meschiari, M.; Franceschini, E.; Bedini, A.; Ferrari, F.; Gennari, W.; Sarti, M.; Mussini, C.
abstract

We compared 90-90-90 targets in 2020, during the coronavirus disease 2019 (COVID-19) pandemic, with the targets across the period 2017-2019 in people with HIV. We observed a significant loss in the 90-90-90 objectives in 2020 when compared with 2017-2019 that might be attributable to the COVID-19 crisis.

2021 - The impact of tocilizumab on respiratory support states transition and clinical outcomes in COVID-19 patients. A Markov model multi-state study [Articolo su rivista]
Milic, J.; Banchelli, F.; Meschiari, M.; Franceschini, E.; Ciusa, G.; Gozzi, L.; Volpi, S.; Faltoni, M.; Franceschi, G.; Iadisernia, V.; Yaacoub, D.; Dolci, G.; Bacca, E.; Rogati, C.; Tutone, M.; Burastero, G.; Raimondi, A.; Menozzi, M.; Cuomo, G.; Corradi, L.; Orlando, G.; Santoro, A.; Digaetano, M.; Puzzolante, C.; Carli, F.; Bedini, A.; Busani, S.; Girardis, M.; Cossarizza, A.; Miglio, R.; Mussini, C.; Guaraldi, G.; D'Amico, R.
abstract

Background The benefit of tocilizumab on mortality and time to recovery in people with severe COVID pneumonia may depend on appropriate timing. The objective was to estimate the impact of tocilizumab administration on switching respiratory support states, mortality and time to recovery. Methods In an observational study, a continuous-time Markov multi-state model was used to describe the sequence of respiratory support states including: no respiratory support (NRS), oxygen therapy (OT), non-invasive ventilation (NIV) or invasive mechanical ventilation (IMV), OT in recovery, NRS in recovery. Results Two hundred seventy-one consecutive adult patients were included in the analyses contributing to 695 transitions across states. The prevalence of patients in each respiratory support state was estimated with stack probability plots, comparing people treated with and without tocilizumab since the beginning of the OT state. A positive effect of tocilizumab on the probability of moving from the invasive and non-invasive mechanical NIV/IMV state to the OT in recovery state (HR = 2.6, 95% CI = 1.2–5.2) was observed. Furthermore, a reduced risk of death was observed in patients in NIV/IMV (HR = 0.3, 95% CI = 0.1–0.7) or in OT (HR = 0.1, 95% CI = 0.0–0.8) treated with tocilizumab. Conclusion To conclude, we were able to show the positive impact of tocilizumab used in different disease stages depicted by respiratory support states. The use of the multi-state Markov model allowed to harmonize the heterogeneous mortality and recovery endpoints and summarize results with stack probability plots. This approach could inform randomized clinical trials regarding tocilizumab, support disease management and hospital decision making.

2021 - The relationship between smoking, current CD4, viral load and cancer in persons living with HIV [Articolo su rivista]
Mocroft, A; Petoumenos, ; Wit, F; J Vehreschild, J; Guaraldi, G; M Miro, J; Greenberg, L; Oellinger, A; Egle, A; F Günthard, H; C Bucher, H; De Wit, S; Necsoi, C; Castagna, A; Spagnuolo, V; D’Arminio Monforte, A; Reiss, P; Chkhartishvili, N; Bolokadze, N; Hoy, J; Sonnenborg, A; Svedhem, V; Bower, M; Volny-Anne, A; Garges, H; Rogatto, F; Neesgaard, B; Peters, L; D Lundgren, J; Ryom, L
abstract

It is unknown if the carcinogenic effect of smoking is influenced by CD4 count and viral load (VL) in persons living with HIV.

2021 - Twenty-four-hour serum creatinine variation is associated with poor outcome in the novel coronavirus disease 2019 (COVID-19) patients [Articolo su rivista]
Alfano, Gaetano; Ferrari, Annachiara; Fontana, Francesco; Mori, Giacomo; Ligabue, Giulia; Giovanella, Silvia; Magistroni, Riccardo; Meschiari, Marianna; Franceschini, Erica; Menozzi, Marianna; Cuomo, Gianluca; Orlando, Gabriella; Santoro, Antonella; Di Gaetano, Margherita; Puzzolante, Cinzia; Carli, Federica; Bedini, Andrea; Milic, Jovana; Mussini, Cristina; Cappelli, Gianni; Guaraldi, Giovanni
abstract

Background: The prognostic value of within-day sCr variation serum creatinine variation is unknown in the setting of the novel coronavirus disease 2019 (COVID-19). We evaluated the prognostic significance of 24-hour serum creatinine variation in COVID-19 patients.Methods: A monocentric retrospective analysis was conducted in COVID-19 patients not admitted to the intensive care unit. Three groups were subdivided based on 24 hours serum creatinine variation from admission. In the stable kidney function group, 24-hour serum creatinine variation ranged from +0.05 to -0.05 mg/dL; in the decreased kidney function group, 24-hour serum creatinine variation was >0.05 mg/dL; in the improved kidney function group, 24-hour serum creatinine variation was <-0.05 mg/dL.Results: The study population included 224 patients with a median age of 66.5 years and a predominance of males (72.3%). Within 24 hours of admission, renal function remained stable in 37.1% of the subjects, whereas it displayed improved and deteriorated patterns in 45.5% and 17.4%, respectively. Patients with decreased kidney function were older and had more severe COVID-19 symptoms than patients with stable or improved kidney function. About half of patients with decreased kidney function developed an episode of acute kidney injury (AKI) during hospitalization. Decreased kidney function was significantly associated with AKI during hospitalization (hazard ratio [HR], 4.6; 95% confidence interval [CI], 1.9-10.8; p < 0.001) and was an independent risk factor for 30-day in-hospital mortality (HR, 5.5; 95% CI, 1.1-28; p = 0.037).Conclusion: COVID-19 patients with decreased kidney function within 24 hours of admission were at high risk of AKI and 30-day in-hospital mortality.

2021 - Two fatal cases of acute liver failure due to HSV-1 infection in COVID-19 patients following immunomodulatory therapies. [Articolo su rivista]
Busani, S; Bedini, A; Biagioni, E; Serio, L; Tonelli, R; Meschiari, M; Franceschini, E; Guaraldi, G; Cossarizza, A; Clini, E; Maiorana, A; Gennari, W; De Maria, N; Luppi, M; Mussini, C; Girardis, M.; Gibellini, Lara
abstract

We reported two fatal cases of acute liver failure secondary to Herpes Simplex Virus 1 infection in COVID-19 patients, following tocilizumab and corticosteroid therapy. Screening for and prompt recognition of Herpes Simplex Virus 1 reactivation in these patients, undergoing immunomodulatory treatment, may have potentially relevant clinical consequences.

2021 - Voice assistance to develop a participatory research and action to improve health trajectories of people with PACS [Abstract in Atti di Convegno]
Caselgrandi, Agnese; Milić, Jovana; Motta, Federico; Belli, Michela; Venuta, Maria; Aprile, Emanuele; Gozzi, Licia; Burastero, Giulia; Iadisernia, Vittorio; Yaacoub, Dina; Orsini, M.; Pacchioni, M.; Mescoli, E.; Mussini, Cristina; Guaraldi, Giovanni
abstract

2021 - Weight gain during pregnancy in women with HIV receiving different antiretroviral regimens [Articolo su rivista]
Floridia, Marco; Masuelli, Giulia; Tassis, Beatrice; Franceschetti, Laura; Savasi, Valeria M; Spinillo, Arsenio; Tamburrini, Enrica; Guaraldi, Giovanni; Dalzero, Serena; Sansone, Matilde; Chiodo, Antonella; Degliantoni, Anna M; Pinnetti, Carmela; Liuzzi, Giuseppina; Ravizza, Marina
abstract

No published studies have evaluated in pregnant women with HIV weight gain with different antiretroviral drug classes.

2020 - A patient-centred approach to deprescribing antiretroviral therapy in people living with HIV [Articolo su rivista]
Guaraldi, Giovanni; Milić, Jovana; Marcotullio, Simone; Mussini, Cristina
abstract

2020 - Abdominal Visceral Infarction in 3 Patients with COVID-19 [Articolo su rivista]
Besutti, G.; Bonacini, R.; Iotti, V.; Marini, G.; Riva, N.; Dolci, G.; Maiorana, M.; Spaggiari, L.; Monelli, F.; Ligabue, G.; Guaraldi, G.; Rossi, P. G.; Pattacini, P.; Massari, M.
abstract

A high incidence of thrombotic events has been reported in patients with coronavirus disease (COVID-19), which is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. We report 3 clinical cases of patients in Italy with COVID-19 who developed abdominal viscera infarction, demonstrated by computed tomography.

2020 - Acute myocarditis as the main clinical manifestation of SARS-CoV 2 infection: A case report [Articolo su rivista]
Cuomo, G.; Menozzi, M.; Carli, F.; Digaetano, M.; Raimondi, A.; Reggianini, L.; Ligabue, G.; Guaraldi, G.; Mussini, C.
abstract

We describe a case of acute myocarditis which was reported as the main COVID-19 clinical manifestation, with a favorable outcome. In addition to symptoms, laboratory tests (BNP and troponin), echocardiogram and cardiac MRI contributed to diagnosis. Regardless heart biopsy was not obtained, it is likely an immunological pathogenesis of this condition which pave the way to further therapeutic implications, since there are currently no standardized treatments.

2020 - Altered bioenergetics and mitochondrial dysfunction of monocytes in patients with COVID-19 pneumonia [Articolo su rivista]
Gibellini, L.; De Biasi, S.; Paolini, A.; Borella, R.; Boraldi, F.; Mattioli, M.; Lo Tartaro, D.; Fidanza, L.; Caro-Maldonado, A.; Meschiari, M.; Iadisernia, V.; Bacca, E.; Riva, G.; Cicchetti, L.; Quaglino, D.; Guaraldi, G.; Busani, S.; Girardis, M.; Mussini, C.; Cossarizza, A.
abstract

In patients infected by SARS-CoV-2 who experience an exaggerated inflammation leading to pneumonia, monocytes likely play a major role but have received poor attention. Thus, we analyzed peripheral blood monocytes from patients with COVID-19 pneumonia and found that these cells show signs of altered bioenergetics and mitochondrial dysfunction, had a reduced basal and maximal respiration, reduced spare respiratory capacity, and decreased proton leak. Basal extracellular acidification rate was also diminished, suggesting reduced capability to perform aerobic glycolysis. Although COVID-19 monocytes had a reduced ability to perform oxidative burst, they were still capable of producing TNF and IFN-γ in vitro. A significantly high amount of monocytes had depolarized mitochondria and abnormal mitochondrial ultrastructure. A redistribution of monocyte subsets, with a significant expansion of intermediate/pro-inflammatory cells, and high amounts of immature monocytes were found, along with a concomitant compression of classical monocytes, and an increased expression of inhibitory checkpoints like PD-1/PD-L1. High plasma levels of several inflammatory cytokines and chemokines, including GM-CSF, IL-18, CCL2, CXCL10, and osteopontin, finally confirm the importance of monocytes in COVID-19 immunopathogenesis.

2020 - Application of guidelines for the management of nonalcoholic fatty liver disease in three prospective cohorts of HIV-monoinfected patients [Articolo su rivista]
Sebastiani, G; Cocciolillo, S; Mazzola, G; Malagoli, A; Falutz, J; Cervo, Andrea; Petta, S; Pembroke, T; Ghali, P; Besutti, Giulia; Franconi, Iacopo; Milić, Jovana; Cascio, Antonio; Guaraldi, G
abstract

Current guidelines recommend use of a diagnostic algorithm to assess disease severity in cases of suspected nonalcoholic fatty liver disease (NAFLD). We applied this algorithm to HIV-monoinfected patients.

2020 - Author's Response [Articolo su rivista]
Alfano, Gaetano; Fontana, Francesco; Guaraldi, Giovanni; Cappelli, Gianni
abstract

2020 - Common cardiovascular risk factors and in-hospital mortality in 3,894 patients with COVID-19: survival analysis and machine learning-based findings from the multicentre Italian CORIST Study [Articolo su rivista]
Di Castelnuovo, A.; Bonaccio, M.; Costanzo, S.; Gialluisi, A.; Antinori, A.; Berselli, Nausicaa; Blandi, L.; Bruno, R.; Cauda, R.; Guaraldi, Giovanni; My, I.; Menicanti, L.; Parruti, G.; Patti, G.; Perlini, S.; Santilli, F.; Signorelli, C.; Stefanini, G. G.; Vergori, A.; Abdeddaim, A.; Ageno, W.; Agodi, A.; Agostoni, P.; Aiello, L.; Al Moghazi, S.; Aucella, F.; Barbieri, G.; Bartoloni, A.; Bologna, C.; Bonfanti, P.; Brancati, S.; Cacciatore, F.; Caiano, L.; Cannata, F.; Carrozzi, L.; Cascio, A.; Cingolani, A.; Cipollone, F.; Colomba, C.; Crisetti, A.; Crosta, F.; Danzi, G. B.; D'Ardes, D.; de Gaetano Donati, K.; Di Gennaro, F.; Di Palma, G.; Di Tano, G.; Fantoni, M.; Filippini, Tommaso; Fioretto, P.; Fusco, F. M.; Gentile, I.; Grisafi, L.; Guarnieri, G.; Landi, F.; Larizza, G.; Leone, A.; Maccagni, G.; Maccarella, S.; Mapelli, M.; Maragna, R.; Marcucci, R.; Maresca, G.; Marotta, C.; Marra, L.; Mastroianni, F.; Mengozzi, A.; Menichetti, F.; Milic, Jovana; Murri, R.; Montineri, A.; Mussinelli, R.; Mussini, Cristina.; Musso, M.; Odone, A.; Olivieri, M.; Pasi, E.; Petri, F.; Pinchera, B.; Pivato, C. A.; Pizzi, R.; Poletti, V.; Raffaelli, F.; Ravaglia, C.; Righetti, G.; Rognoni, A.; Rossato, M.; Rossi, M.; Sabena, A.; Salinaro, F.; Sangiovanni, V.; Sanrocco, C.; Scarafino, A.; Scorzolini, L.; Sgariglia, R.; Simeone, P. G.; Spinoni, E.; Torti, C.; Trecarichi, E. M.; Vezzani, F.; Veronesi, G.; Vettor, R.; Vianello, A.; Vinceti, Marco; De Caterina, R.; Iacoviello, L.
abstract

Background and aims: There is poor knowledge on characteristics, comorbidities and laboratory measures associated with risk for adverse outcomes and in-hospital mortality in European Countries. We aimed at identifying baseline characteristics predisposing COVID-19 patients to in-hospital death. Methods and results: Retrospective observational study on 3894 patients with SARS-CoV-2 infection hospitalized from February 19th to May 23rd, 2020 and recruited in 30 clinical centres distributed throughout Italy. Machine learning (random forest)-based and Cox survival analysis. 61.7% of participants were men (median age 67 years), followed up for a median of 13 days. In-hospital mortality exhibited a geographical gradient, Northern Italian regions featuring more than twofold higher death rates as compared to Central/Southern areas (15.6% vs 6.4%, respectively). Machine learning analysis revealed that the most important features in death classification were impaired renal function, elevated C reactive protein and advanced age. These findings were confirmed by multivariable Cox survival analysis (hazard ratio (HR): 8.2; 95% confidence interval (CI) 4.6–14.7 for age ≥85 vs 18–44 y); HR = 4.7; 2.9–7.7 for estimated glomerular filtration rate levels <15 vs ≥ 90 mL/min/1.73 m2; HR = 2.3; 1.5–3.6 for C-reactive protein levels ≥10 vs ≤ 3 mg/L). No relation was found with obesity, tobacco use, cardiovascular disease and related-comorbidities. The associations between these variables and mortality were substantially homogenous across all sub-groups analyses. Conclusions: Impaired renal function, elevated C-reactive protein and advanced age were major predictors of in-hospital death in a large cohort of unselected patients with COVID-19, admitted to 30 different clinical centres all over Italy.

2020 - COVID-19-associated vasculitis and thrombotic complications: from pathological findings to multidisciplinary discussion [Articolo su rivista]
Vacchi, Caterina; Meschiari, Marianna; Milic, Jovana; Marietta, Marco; Tonelli, Roberto; Alfano, Gaetano; Volpi, Sara; Faltoni, Matteo; Franceschi, Giacomo; Ciusa, Giacomo; Bacca, Erica; Tutone, Marco; Raimondi, Alessandro; Menozzi, Marianna; Franceschini, Erica; Cuomo, Gianluca; Orlando, Gabriella; Santoro, Antonella; Di Gaetano, Margherita; Puzzolante, Cinzia; Carli, Federica; Bedini, Andrea; Cossarizza, Andrea; Castaniere, Ivana; Ligabue, Guido; De Ruvo, Nicola; Manco, Gianrocco; Rolando, Giovanni; Gelmini, Roberta; Maiorana, Antonino; Girardis, Massimo; Mascia, Maria Teresa; Mussini, Cristina; Salvarani, Carlo; Guaraldi, Giovanni
abstract

Neutrophilic arterial vasculitis in COVID-19 represents a novel finding and could be responsible for thrombotic complications.

2020 - Data-driven vs knowledge-driven inference of health outcomes in the ageing population: A case study [Relazione in Atti di Convegno]
Ferrari, D.; Guaraldi, G.; Mandreoli, F.; Martoglia, R.; Milić, Jovana; Missier, Paolo
abstract

Preventive, Predictive, Personalised and Participative (P4) medicine has the potential to not only vastly improve people's quality of life, but also to significantly reduce healthcare costs and improve its efficiency. Our research focuses on age-related diseases and explores the opportunities offered by a data-driven approach to predict wellness states of ageing individuals, in contrast to the commonly adopted knowledge-driven approach that relies on easy-to-interpret metrics manually introduced by clinical experts. This is done by means of machine learning models applied on the My Smart Age with HIV (MySAwH) dataset, which is collected through a relatively new approach especially for older HIV patient cohorts. This includes Patient Related Outcomes values from mobile smartphone apps and activity traces from commercial-grade activity loggers. Our results show better predictive performance for the data-driven approach. We also show that a post hoc interpretation method applied to the predictive models can provide intelligible explanations that enable new forms of personalised and preventive medicine.

2020 - Effects of atazanavir, darunavir, and raltegravir on fat and muscle among persons living with HIV [Articolo su rivista]
Adrian, S.; Miao, H.; Feng, H.; Scherzinger, A.; Nardini, G.; Beghetto, B.; Roncaglia, E.; Ligabue, G.; Milic, J.; Guaraldi, G.; Lake, J. E.; Erlandson, K. M.
abstract

Background: Antiretroviral therapy (ART) is associated with gain in quantity of fat and muscle, but the impact on quality is less understood. The objective of this study was to compare fat and muscle density among people with HIV (PWH) on stable raltegravir (RAL), atazanavir with ritonavir (ATV/r), or darunavir with ritonavir (DRV/r), and explore implications on muscle function. Methods: Participants from the Modena HIV Metabolic Clinic taking RAL, ATV/r, or DRV/r with at least 1 computed tomography (CT) scan were included. CT scans were reanalyzed for area and density of truncal fat and musculature. Multivariate models explored the effect of ART on fat and muscle density. Results: One hundred six participants were receiving ATV/r, 48 DRV/r, and 141 RAL. In multivariate models (reference ATV/r), only DRV/r was associated with greater subcutaneous (SAT) and visceral adipose tissue (VAT) area, lower lateralis muscle density (more fat), and greater lateralis intermuscular fat area. Compared to ATV/r, RAL was independently associated with less psoas intermuscular fat area. Among all, greater paraspinal muscle density correlated with better physical function. No associations between ART group and physical function were seen among men; DRV/r was associated with stronger grip strength among women. Conclusion: DRV/r was associated with greater fat area and lower density of both fat and muscle, and RAL with less intermuscular psoas fat. Higher density psoas and paraspinal musculature were associated with better physical function, suggesting potential clinical relevance of these findings.

2020 - Efficient T cell compartment in HIV+ patients receiving orthotopic liver transplant and immunosuppressive therapy [Articolo su rivista]
Franceschini, Erica; De Biasi, Sara; Digaetano, Margherita; Bianchini, Elena; Lo Tartaro, Domenico; Gibellini, Lara; Menozzi, Marianna; Zona, Stefano; Tarantino, Giuseppe; Nasi, Milena; Codeluppi, Mauro; Guaraldi, Giovanni; Magistri, Paolo; Di Benedetto, Fabrizio; Pinti, Marcello; Mussini, Cristina; Cossarizza, Andrea
abstract

In patients undergoing orthotopic liver transplant (OLT), immunosuppressive (IS) treatment is mandatory and infections are leading causes of morbidity/mortality. Thus, it is essential to understand the functionality of cell-mediated immunity after OLT. The aim of the study was to identify changes in T cell phenotype and polyfunctionality in HIV+ and HIV- patients treated with IS after OLT.

2020 - Epidemiology and Outcomes of Bloodstream Infections in HIV-Patients during a 13-Year Period [Articolo su rivista]
Franceschini, E.; Santoro, Antonella; Menozzi, Marianna; Bacca, Erica; Venturelli, Claudia; Zona, Stefano; Bedini, Andrea; Digaetano, Margherita; Puzzolante, Cinzia; Meschiari, Marianna; Cuomo, Gianluca; Orlando, Gabriella; Sarti, Mario; Guaraldi, Giovanni; Cozzi-Lepri, Alessandro; Mussini, Cristina
abstract

2020 - Epidemiology and Risk Factors Associated with Mortality in Consecutive Patients with Bacterial Bloodstream Infection: Impact of MDR and XDR Bacteria [Articolo su rivista]
Santoro, A.; Franceschini, E.; Meschiari, M.; Menozzi, M.; Zona, S.; Venturelli, C.; Digaetano, M.; Rogati, C.; Guaraldi, G.; Paul, M.; Gyssens, I. C.; Mussini, C.
abstract

Background. Mortality related to bloodstream infections (BSIs) is high. The epidemiology of BSIs is changing due to the increase in multidrug resistance, and it is unclear whether the presence of multidrug-resistant (MDR) organisms, per se, is an independent risk factor for mortality. Our objectives were, first, to describe the epidemiology and outcome of BSIs and, second, to determine the risk factors associated with mortality among patients with BSI. Methods. This research used a single-center retrospective observational study design. Patients were identified through microbiological reports. Data on medical history, clinical condition, bacteria, antimicrobial therapy, and mortality were collected. The primary outcome was crude mortality at 30 days. The relationships between mortality and demographic, clinical, and microbiological variables were analyzed by multivariate analysis. Results. A total of 1049 inpatients were included. MDR bacteria were isolated in 27.83% of patients, where 2.14% corresponded to an extremely drug-resistant (XDR) isolate. The crude mortality rates at days 7, 30, and 90 were 12.11%, 25.17%, and 36.13%, respectively. Pitt score >2, lung and abdomen as site of infection, and XDR Pseudomonas aeruginosa were independent risk factors for 7-, 30-, and 90-day mortality. Charlson score >4, carbapenem-resistant Klebsiella pneumoniae, and XDR Acinetobacter baumannii were independent risk factors for 30- and 90-day mortality. Infection by XDR gram-negative bacteria, Charlson score >4, and immunosuppression were independent risk factors for mortality in patients who were stable at the time of BSI. Conclusions. BSI is an event with an extreme impact on mortality. Patients with severe clinical condition are at higher risk of death. The presence of XDR gram-negative bacteria in blood is strongly and independently associated with patient death.

2020 - Evaluation of HIV transmission clusters among natives and foreigners living in Italy [Articolo su rivista]
Fabeni, L.; Santoro, M. M.; Lorenzini, P.; Rusconi, S.; Gianotti, N.; Costantini, A.; Sarmati, L.; Antinori, A.; Ceccherini-Silberstein, F.; d'Arminio Monforte, A.; Saracino, A.; Girardi, E.; Castagna, A.; Castelli, F.; Cauda, R.; Di Perri, G.; Galli, M.; Iardino, R.; Ippolito, G.; Lazzarin, A.; Marchetti, G. C.; Rezza, G.; von Schloesser, F.; Viale, P.; Cozzi-Lepri, A.; Gori, A.; Lo Caputo, S.; Maggiolo, F.; Mussini, C.; Puoti, M.; Perno, C. F.; Bai, F.; Bandera, A.; Bonora, S.; Borderi, M.; Calcagno, A.; Capobianchi, M. R.; Cicalini, S.; Cingolani, A.; Cinque, P.; Di Biagio, A.; Gagliardini, R.; Guaraldi, G.; Lapadula, G.; Lichtner, M.; Lai, A.; Madeddu, G.; Merlini, E.; Nozza, S.; Piconi, S.; Pinnetti, C.; Quiros Roldan, E.; Rossotti, R.; Spagnuolo, V.; Svicher, V.; Taramasso, L.; Fanti, I.; Galli, L.; Rodano, A.; Macchia, M.; Tavelli, A.; Bove, A.; Camposeragna, A.; Errico, M.; Manfredini, M.; Perziano, A.; Calvino, V.; Carrara, S.; Di Caro, A.; Graziano, S.; Petroni, F.; Prota, G.; Truffa, S.; Giacometti, A.; Barocci, V.; Angarano, G.; Monno, L.; Milano, E.; Suardi, C.; Donati, V.; Verucchi, G.; Castelnuovo, F.; Minardi, C.; Menzaghi, B.; Abeli, C.; Chessa, L.; Pes, F.; Cacopardo, B.; Celesia, B.; Vecchiet, J.; Falasca, K.; Pan, A.; Lorenzotti, S.; Sighinolfi, L.; Segala, D.; Blanc, P.; Vichi, F.; Cassola, G.; Bassetti, M.; Alessandrini, A.; Bobbio, N.; Mazzarello, G.; Fondaco, L.; Bonfanti, P.; Molteni, C.; Chiodera, A.; Milini, P.; Nunnari, G.; Pellicano, G.; Rizzardini, G.; Cannizzo, E. S.; Moioli, M. C.; Piolini, R.; Bernacchia, D.; Poli, A.; Tincati, C.; Puzzolante, C.; Migliorino, C.; Sangiovanni, V.; Borgia, G.; Esposito, V.; Di Flumeri, G.; Gentile, I.; Rizzo, V.; Cattelan, A. M.; Marinello, S.; Cascio, A.; Trizzino, M.; Francisci, D.; Schiaroli, E.; Parruti, G.; Sozio, F.; Lazzaretti, C.; Corsini, R.; Cristaudo, A.; Vullo, V.; Acinapura, R.; Lamonica, S.; Capozzi, M.; Mondi, A.; Rivano Capparuccia, M.; Iaiani, G.; Latini, A.; Onnelli, G.; Plazzi, M. M.; de Girolamo, G.; Vergori, A.; Cecchetto, M.; Viviani, F.; de Vito, A.; Rossetti, B.; Montagnani, F.; Franco, A.; Fontana Del Vecchio, R.; Di Giuli, C.; Caramello, P.; Orofino, G. C.; Sciandra, M.; Londero, A.; Manfrin, V.; Battagin, G.; Starnini, G.; Ialungo, A.
abstract

We aimed at evaluating the characteristics of HIV-1 molecular transmission clusters (MTCs) among natives and migrants living in Italy, diagnosed between 1998 and 2018. Phylogenetic analyses were performed on HIV-1 polymerase (pol) sequences to characterise subtypes and identify MTCs, divided into small (SMTCs, 2-3 sequences), medium (MMTCs, 4-9 sequences) and large (LMTCs, ≥10 sequences). Among 3499 drug-naïve individuals enrolled in the Italian Cohort Naive Antiretroviral (ICONA) cohort (2804 natives; 695 migrants), 726 (20.8%; 644 natives, 82 migrants) were involved in 228 MTCs (6 LMTCs, 36 MMTCs, 186 SMTCs). Migrants contributed 14.4% to SMTCs, 7.6% to MMTCs and 7.1% to LMTCs, respectively. HIV-1 non-B subtypes were found in 51 MTCs; noteworthy was that non-B infections involved in MTCs were more commonly found in natives (n = 47) than in migrants (n = 4). Factors such as Italian origin, being men who have sex with men (MSM), younger age, more recent diagnosis and a higher CD4 count were significantly associated with MTCs. Our findings show that HIV-1 clustering transmission among newly diagnosed individuals living in Italy is prevalently driven by natives, mainly MSM, with a more recent diagnosis and frequently infected with HIV-1 non-B subtypes. These results can contribute to monitoring of the HIV epidemic and guiding the public health response to prevent new HIV infections.

2020 - Expansion of plasmablasts and loss of memory B cells in peripheral blood from COVID-19 patients with pneumonia [Articolo su rivista]
De Biasi, S.; Lo Tartaro, D.; Meschiari, M.; Gibellini, L.; Bellinazzi, C.; Borella, R.; Fidanza, L.; Mattioli, M.; Paolini, A.; Gozzi, L.; Jaacoub, D.; Faltoni, M.; Volpi, S.; Milic, J.; Sita, M.; Sarti, M.; Pucillo, C.; Girardis, M.; Guaraldi, G.; Mussini, C.; Cossarizza, A.
abstract

Studies on the interactions between SARS-CoV-2 and humoral immunity are fundamental to elaborate effective therapies including vaccines. We used polychromatic flow cytometry, coupled with unsupervised data analysis and principal component analysis (PCA), to interrogate B cells in untreated patients with COVID-19 pneumonia. COVID-19 patients displayed normal plasma levels of the main immunoglobulin classes, of antibodies against common antigens or against antigens present in common vaccines. However, we found a decreased number of total and naïve B cells, along with decreased percentages and numbers of memory switched and unswitched B cells. On the contrary, IgM+ and IgM− plasmablasts were significantly increased. In vitro cell activation revealed that B lymphocytes showed a normal proliferation index and number of dividing cells per cycle. PCA indicated that B-cell number, naive and memory B cells but not plasmablasts clustered with patients who were discharged, while plasma IgM level, C-reactive protein, D-dimer, and SOFA score with those who died. In patients with pneumonia, the derangement of the B-cell compartment could be one of the causes of the immunological failure to control SARS-Cov2, have a relevant influence on several pathways, organs and systems, and must be considered to develop vaccine strategies.

2020 - Feasibility and clinical impact of out-of-ICU noninvasive respiratory support in patients with COVID-19-related pneumonia [Articolo su rivista]
Franco, C; Facciolongo, N; Tonelli, R; Dongilli, R; Vianello, A; Pisani, L; Scala, R; Malerba, M; Carlucci, A; Negri, Ea; Spoladore, G; Arcaro, G; Tillio, Pa; Lastoria, C; Schifino, G; Tabbi', L; Guidelli, L; Guaraldi, G; Ranieri, M; Clini, E; Nava, S.
abstract

Introduction: The Coronavirus 2(SARS-CoV-2) outbreak spread rapidly in Italy and the lack of intensive care unit(ICU) beds soon became evident, forcing the application of noninvasive respiratory support(NRS) outside the ICU, raising concerns over staff contamination. We aimed to analyze the safety of the hospital staff, the feasibility, and outcomes of NRS applied to patients outside the ICU. Methods: In this observational study, data from 670 consecutive patients with confirmed COVID-19 referred to the Pulmonology Units in nine hospitals between March 1st and May 10th,2020 were analyzed. Data were collected including medication, mode and usage of the NRS (i.e. high-flow nasal cannula (HFNC), continuous positive airway pressure (CPAP), noninvasive ventilation(NIV)), length of stay in hospital, endotracheal intubation(ETI) and deaths. Results: Forty-two health-care workers (11.4%) tested positive for infection, but only three of them required hospitalization. Data are reported for all patients (69.3% male), whose mean age was 68 (SD 13) years. The PaO2/FiO2 ratio at baseline was 152+79, and the majority of patients (49.3%) were treated with CPAP. The overall unadjusted 30-day mortality rate was 26.9% with 16%, 30%, and 30%, while the total ETI rate was 27% with 29%, 25% and 28%, for HFNC, CPAP, and NIV, respectively, and the relative probability to die was not related to the NRS used after adjustment for confounders. ETI and length of stay were not different among the groups. Mortality rate increased with age and comorbidity class progression. Conclusions: The application of NRS outside the ICU is feasible and associated with favourable outcomes. Nonetheless, it was associated with a risk of staff contamination.

2020 - Handling and processing of blood specimens from patients with Covid-19 for safe studies on cell phenotype and cytokine storm [Articolo su rivista]
Cossarizza, Andrea; Gibellini, Lara; DE BIASI, Sara; LO TARTARO, Domenico; Mattioli, Marco; Paolini, Annamaria; Fidanza, Lucia; Bellinazzi, Caterina; Borella, Rebecca; Castaniere, Ivana; Meschiari, Marianna; Sita, Marco; Manco, Gianrocco; Clini, Enrico; Gelmini, Roberta; Girardis, Massimo; Guaraldi, Giovanni; Mussini, Cristina
abstract

The pandemic caused by SARS-CoV-2 heavily involves all those working in a laboratory. Samples from known infected patients or donors who are considered healthy can arrive, and a colleague might be asymptomatic but able to transmit the virus. Working in a clinical laboratory is posing several safety challenges. Few years ago, ISAC published guidelines to safely analyze and sort human samples that were revised in these days. We describe the procedures that we have been following since the first patient appeared in Italy, which have only slightly modified our standard one, being all human samples associated with risks.

2020 - Human immunodeficiency virus continuum of care in 11 european union countries at the end of 2016 overall and by key population: Have we made progress? [Articolo su rivista]
Vourli, G.; Noori, T.; Pharris, A.; Porter, K.; Axelsson, M.; Begovac, J.; Cazein, F.; Costagliola, D.; Cowan, S.; Croxford, S.; Monforte, A. D.; Delpech, V.; Diaz, A.; Girardi, E.; Gunsenheimer-Bartmeyer, B.; Hernando, V.; Leierer, G.; Lot, F.; Nunez, O.; Obel, N.; Op de Coul, E.; Paraskeva, D.; Patrinos, S.; Reiss, P.; Schmid, D.; Sonnerborg, A.; Suligoi, B.; Supervie, V.; van Sighem, A.; Zangerle, R.; Touloumi, G.; Egle, A.; Kanatschnig, M.; Ollinger, A.; Rieger, A.; Schmied, B.; Wallner, E.; Dewasurendra, D.; Gisinger, M.; Kitchen, M.; Plattner, A.; Rieser, E.; Sarcletti, M.; Greil, R.; Schachner, M.; Skocic, M.; Muller, M.; Aichwalder, R.; Chromy, D.; Grabmeier-Pfstershammer, K.; Skoll, M.; Touzeau, V.; Cichon, P.; Wolf-Nussmuller, S.; Laferl, H.; Zoufaly, A.; Genger-Hackl, C.; Kapper, A.; Schneeberger, T.; Trattner, E.; Schober, G.; Atzl, M.; Hartmann, B.; Puchhammer-Stockl, E.; Berg, J.; Appoyer, H.; Rappold, M.; Strickner, S.; Schindelwig, K.; Ledergerber, B.; Fatkenheuer, G.; Gerstof, J.; Kronborg, G.; Pedersen, C.; Larsen, C. S.; Pedersen, G.; Mohey, R.; Nielsen, L.; Weise, L.; Kvinesdal, B.; Jensen, J.; Abgrall, S.; Bernard, L.; Billaud, E.; Boue, F.; Boyer, L.; Cabie, A.; Caby, F.; Canestri, A.; Cotte, L.; de Truchis, P.; Duval, X.; Duvivier, C.; Enel, P.; Fischer, H.; Gasnault, J.; Gaud, C.; Grabar, S.; Khuong-Josses, M. A.; Launay, O.; Marchand, L.; Mary-Krause, M.; Matheron, S.; Melica-Gregoire, G.; Melliez, H.; Meynard, J. L.; Nacher, M.; Pavie, J.; Piroth, L.; Poizot-Martin, I.; Pradier, C.; Reynes, J.; Rouveix, E.; Simon, A.; Slama, L.; Tattevin, P.; Tissot-Dupont, H.; Biga, J.; Kurth, T.; Jacquemet, N.; Guiguet, M.; Leclercq, S.; Lievre, L.; Marshall, E.; Roul, H.; Selinger-Leneman, H.; Potard, V.; Benveniste, O.; Breton, G.; Lupin, C.; Bourzam, E.; Girard, P. M.; Fonquernie, L.; Valin, N.; Lefebvre, B.; Sebire, M.; Pialoux, G.; Lebrette, M. G.; Tibaut, P.; Adda, A.; Hamidi, M.; Cadranel, J.; Lavole, A.; Parrot, A.; Bouchaud, O.; Vignier, N.; Mechai, F.; Makhlouf, S.; Honore, P.; Bergmann, J. F.; Delcey, V.; Lopes, A.; Sellier, P.; Parrinello, M.; Oksenhendler, E.; Gerard, L.; Molina, J. M.; Rozenbaum, W.; Denis, B.; De Castro, N.; Lascoux, C.; Yazdanpanah, Y.; Lariven, S.; Joly, V.; Rioux, C.; Poupard, M.; Taverne, B.; Sutton, L.; Masse, V.; Genet, P.; Wifaq, B.; Gerbe, J.; Grefe, S.; Dupont, C.; Freire Maresca, A.; Reimann, E.; Bloch, M.; Meier, F.; Mortier, E.; Zeng, F.; Montoya, B.; Perronne, C.; Mathez, D.; Marigot-Outtandy, D.; Berthe, H.; Greder Belan, A.; Terby, A.; Godin Collet, C.; Marque Juillet, S.; Ruquet, M.; Roussin-Bretagne, S.; Colardelle, P.; Granier, F.; Laurichesse, J. J.; Perronne, V.; Akpan, T.; Marcou, M.; Daneluzzi, V.; Veyssier-Belot, C.; Masson, H.; Welker, Y.; Brazille, P.; Kahn, J. E.; Zucman, D.; Majerholc, C.; Fourn, E.; Bornarel, D.; Chambrin, V.; Kansau, I.; Raho-Moussa, M.; Lelievre, J. D.; Saidani, M.; Chesnel, C.; Dumont, C.; Vittecoq, D.; Derradji, O.; Bolliot, C.; Goujard, C.; Teicher, E.; Mole, M.; Bourdic, K.; Salmon, D.; Le Jeunne, C.; Guet, P.; Pietri, M. P.; Pannier Metzger, E.; Marcou, V.; Loulergue, P.; Dupin, N.; Morini, J. P.; Deleuze, J.; Gerhardt, P.; Chanal, J.; Weiss, L.; Lucas, M. L.; Jung, C.; Ptak, M.; Viard, J. P.; Ghosn, J.; Gazalet, P.; Cros, A.; Maignan, A.; Lortholary, O.; Rouzaud, C.; Touam, F.; Benhadj, K.; Consigny, P. H.; Bossi, P.; Gergely, A.; Cessot, G.; Durand, F.; Beck-Wirth, G.; Michel, C.; Benomar, M.; Rey, D.; Partisani, M.; Cheneau, C.; Batard, M. L.; Fischer, P.; Leclercq, P.; Blanc, M.; Morand, P.; Epaulard, O.; Signori-Schmuck, A.; Laurichesse, H.; Jacomet, C.; Vidal, M.; Coban, D.; Casanova, S.; Fresard, A.; Guglielminotti, C.; Botelho-Nevers, E.; Brunon-Gagneux, A.; Ronat, V.; Verdon, R.; Dargere, S.; Haustraete, E.; Feret, P.; Goubin, P.; Chavanet, P.; Fillion, A.; Croisier, D.; Gohier, S.; Arvieux, C.; Souala, F.; Chapplain, J. M.; Ratajczak, M.; Rohan, J.; Faller, J. P.; Ruyer, O.; Gendrin, V.; Toko, L.; Chirouze, C.; Hustache-Mat
abstract

Background. High uptake of antiretroviral treatment (ART) is essential to reduce human immunodeficiency virus (HIV) transmission and related mortality; however, gaps in care exist. We aimed to construct the continuum of HIV care (CoC) in 2016 in 11 European Union (EU) countries, overall and by key population and sex. To estimate progress toward the Joint United Nations Programme on HIV/AIDS (UNAIDS) 90-90-90 target, we compared 2016 to 2013 estimates for the same countries, representing 73% of the population in the region. Methods. A CoC with the following 4 stages was constructed: number of people living with HIV (PLHIV); proportion of PLHIV diagnosed; proportion of those diagnosed who ever initiated ART; and proportion of those ever treated who achieved viral suppression at their last visit. Results. We estimated that 87% of PLHIV were diagnosed; 92% of those diagnosed had ever initiated ART; and 91% of those ever on ART, or 73% of all PLHIV, were virally suppressed. Corresponding figures for men having sex with men were: 86%, 93%, 93%, 74%; for people who inject drugs: 94%, 88%, 85%, 70%; and for heterosexuals: 86%, 92%, 91%, 72%. The proportion suppressed of all PLHIV ranged from 59% to 86% across countries. Conclusions. The EU is close to the 90-90-90 target and achieved the UNAIDS target of 73% of all PLHIV virally suppressed, significant progress since 2013 when 60% of all PLHIV were virally suppressed. Strengthening of testing programs and treatment support, along with prevention interventions, are needed to achieve HIV epidemic control.

2020 - Implementing routine physical function screening among elderly HIV-positive patients in Uganda* [Articolo su rivista]
Lwanga, I.; Nabaggala, M. S.; Kiragga, A.; Calcagno, A.; Guaraldi, G.; Lamorde, M.; Castelnuovo, B.
abstract

We conducted a cross-sectional study to describe routine physical function assessment for HIV-infected adults aged ≥60 years attending a large urban HIV clinic in Kampala, Uganda. Assessed demographic and clinical factors associated with low physical function in the population, generalized linear regression model was used to estimate factors associated with low physical function. Of the 93 elderly patients that underwent the Short Physical Performance Battery (SPPB) assessment, 43/93 (44.1%) scored 1–8 points at the SPPB evaluation and were categorized as low function, 45/93 (48.4%) scored 9–11 points and were categorized as moderate function and 7/93 (7.5%) scored 12 points and were categorized as high (normal) function. Women (adjusted risk ratio (ARR) 2.57; 95% confidence interval (CI): 1.54–4.29, p = 0.000) had increased risk of low physical function compared to men. A one-year increase in age (ARR = 1.09; CI: 1.03–1.15, p = 0.004) and being overweight (BMI > 25.0, ARR = 1.96; CI: 1.89–3.24, p = 0.008) also carried an increased risk of low physical function status. A higher number 13/41(32%) of falls was recorded in female than among male 3/53(5.8%) patients (p = 0.001). The SPPB assessment is a starting point for clinicians to comprehensively evaluate and consider the management of physical function limitation among older HIV-positive patients.

2020 - Increased BMI and Type 2 diabetes are the main predictors of NAFLD and advanced fibrosis in liver biopsies of patients with HIV mono-infection [Articolo su rivista]
Maurice, James B; Goldin, Robert; Hall, Andrew; Price, Jennifer C; Sebastiani, Giada; Morse, Caryn G; Prat, Laura; Perazzo, Hugo; Garvey, Lucy; Ingiliz, Patrick; Guaraldi, Giovanni; Tsochatzis, Emmanouil; Lemoine, Maud
abstract

Liver disease is an important cause of morbidity and mortality in people living with HIV (PLWH), of which non-alcoholic fatty liver disease (NAFLD) is an increasingly recognised cause. There is limited data investigating NAFLD in HIV mono-infection and histologically defined disease. We aimed to identify who is at risk of fibrosis, NAFLD and NASH among PLWH, and explore the diagnostic accuracy of non-invasive markers of fibrosis.

2020 - Influence of Hepatitis C Coinfection and Treatment on Risk of Diabetes Mellitus in HIV-Positive Persons [Articolo su rivista]
Mocroft, Amanda; Lundgren, Jens D; Rockstroh, Juergen K; Aho, Inka; Wandeler, Gilles; Nielsen, Lars; Edwards, Simon; Viard, Jean-Paul; Lacombe, Karine; Fätkenheuer, Gerd; Guaraldi, Giovanni; Laguno, Montserrat; Llibre, Josep; Elinav, Hila; Flamholc, Leo; Gisinger, Martin; Paduta, Dzmitry; Khromova, Irina; Jilich, David; Rozplochowski, Blazej; Oprea, Cristiana; Peters, Lars
abstract

The role of hepatitis C virus (HCV) coinfection and HCV-RNA in the development of diabetes mellitus (DM) in HIV-positive persons remains unclear.

2020 - Liver steatosis and non-alcoholic fatty liver disease with fibrosis are predictors of frailty in people living with HIV [Articolo su rivista]
Milic, Jovana; Menozzi, Valentina; Schepis, Filippo; Malagoli, Andrea; Besutti, Giulia; Franconi, Iacopo; Raimondi, Alessandro; Carli, Federica; Mussini, Cristina; Sebastiani, Giada; Guaraldi, Giovanni
abstract

2020 - Long-term consequences of COVID-19: research needs [Articolo su rivista]
Yelin, D.; Wirtheim, E.; Vetter, P.; Kalil, A. C.; Bruchfeld, J.; Runold, M.; Guaraldi, G.; Mussini, C.; Gudiol, C.; Pujol, M.; Bandera, A.; Scudeller, L.; Paul, M.; Kaiser, L.; Leibovici, L.
abstract

2020 - Long-term effects of COVID-19 in a patient on maintenance dialysis [Articolo su rivista]
Alfano, G.; Perrone, R.; Fontana, F.; Mori, G.; Lucchi, L.; Guaraldi, G.; Magistroni, R.; Cappelli, G.
abstract

Coronavirus infectious disease (COVID-19) is a novel respiratory infection highly associated with severe complications in elderly subjects affected by cardiovascular disease. Patients on maintenance dialysis are exceptionally vulnerable because most of them are old and have multiple comorbidities. We report the complex clinical course of SARS-CoV-2 infection in a patient on maintenance dialysis who presented with fever and lung edema. After 41 days from the primary infection, the clinically recovered patient experienced symptomatic reactivation of SARS-COV-2 infection documented by positive polymerase chain reaction (PCR) result on nasal/oropharyngeal swab with immunoglobulin M seroconversion. The recurrence of PCR positivity forced us to perform hemodialysis in a separate isolation room for a prolonged period of time. Close monitoring of previously infected patients and restructuring of dialysis facilities are necessary to avoid new outbreaks of this concerning disease.

2020 - Low Serum Testosterone (T) Is Associated with Poor Health Status in Young to Middle-Aged Human Immunodeficiency Virus (HIV)-Infected Men. [Abstract in Atti di Convegno]
De Vincentis, S.; Decaroli, M. C.; Diazzi, C.; Morini, F.; Bertani, D.; Fanelli, F.; Mezzullo, M.; Santi, D.; Tartaro, G.; Baraldi, E.; Tagliavini, S.; Pagotto, U.; Guaraldi, G.; Rochira, V.
abstract

BACKGROUND: The relationship between health status, defined by frailty and comorbidities, and serum T levels has been widely demonstrated in general population, while only one previous retrospective study has explored it in HIV-infected men1. AIM: To investigate the association between frailty and go- nadal status by assessing serum total T (TT) with Liquid Chromatography tandem Mass Spectrometry (LC-MS/MS) in a cohort of HIV-infected men. METHODS: Prospective, cross-sectional, observational study on HIV-infected men (age <50 years) with on- going Highly Active Antiretroviral Therapy. Serum TT was assessed by the gold standard ID-LC-MS/MS. Sex hormone-binding globulin (SHBG) was measured by chem- iluminescent immunoassay. Calculated free T (cFT) was obtained by Vermeulen equation. Multimorbidity was de- fined as at least 3 comorbid conditions, including: hyperten- sion, diabetes, cardiovascular disease, chronic obstructive pulmonary disease, chronic kidney disease, osteoporosis, chronic viral hepatitis and cancers. Frailty was calculated through the validated 37-item frailty index (FI)2. Patients with FI>0.21 were considered frail. Statistical ana- lysis: Mann-Whitney U test was used to compare contin- uous variables. Correlations were performed using linear regression models. RESULTS: 315 consecutive HIV-infected men were enrolled (mean age 45.3±5.3 years; average duration of HIV-infection 16.3±8.8 years). 128 patients (40.5%) were co- morbid and 207 (64.9%) were frail. Either cFT (p=0.001) or TT (p<0.001) were lower in comorbid patients than others. FT was inversely related to the number of comorbidities (p<0.001, R2=0.045). Accordingly, cFT (p=0.003) and TT (p<0.001) were significantly lower in frail patients.Frailty score was inversely correlated with cFT (p<0.001, R2=0.058), TT (p=0.041, R2=0.014) and SHBG (p=0.003, R2=0.029). However, after adjustment for age and duration of HIV-infection, cFT, TT and SHBG were excluded from the regression model. CONCLUSIONS: Low cFT and TT levels are associated with multimorbidity and poor health status in HIV infected men. The bidirectional nature of this relationship leads to the figuration of an intriguing vicious circle where T de- ficiency triggers the onset of comorbidities or, vice versa, poor health status induces hypogonadism. At the same time, notwithstanding the inverse relation between FT and frailty, it seems that other stronger predictive factors, and in particular the duration of infection, are involved in de- termining the health outcome in this clinical setting.

2020 - Machine learning in predicting respiratory failure in patients with COVID-19 pneumonia - challenges, strengths, and opportunities in a global health emergency. [Articolo su rivista]
Ferrari, D; Milic, J; Tonelli, R; Ghinelli, F; Meschiari, M; Volpi, S; Faltoni, M; Franceschi, G; Iadisernia, V; Yaacoub, D; Ciusa, G; Bacca, E; Rogati, C; Tutone, M; Burastero, G; Raimondi, A; Menozzi, M; Franceschini, E; Cuomo, G; Corradi, L; Orlando, G; Santoro, A; Di Gaetano, M; Puzzolante, C; Carli, F; Borghi, V; Bedini, A; Fantini, R; Tabbì, L; Castaniere, I; Busani, S; Clini, E; Girardis, M; Sarti, M; Cossarizza, A; Mussini, C; Mandreoli, F; Missier, P; Guaraldi, G.
abstract

Aims- The aim of this study was to estimate a 48 hour prediction of moderate to severe respiratory failure, requiring mechanical ventilation, in hospitalized patients with COVID-19 pneumonia. Methods- This was an observational study that comprised consecutive patients with COVID-19 pneumonia admitted to hospital from 21 February to 6 April 2020. The patients’ medical history, demographic, epidemiologic and clinical data were collected in an electronic patient chart. The dataset was used to train predictive models using an established machine learning framework leveraging a hybrid approach where clinical expertise is applied alongside a data-driven analysis. The study outcome was the onset of moderate to severe respiratory failure defined as PaO 2 /FiO 2 ratio <150 mmHg in at least one of two consecutive arterial blood gas analyses in the following 48 hours. Shapley Additive exPlanations values were used to quantify the positive or negative impact of each variable included in each model on the predicted outcome. Results- A total of 198 patients contributed to generate 1068 usable observations which allowed to build 3 predictive models based respectively on 31-variables signs and symptoms, 39-variables laboratory biomarkers and 91-variables as a composition of the two. A fourth “boosted mixed model” included 20 variables was selected from the model 3, achieved the best predictive performance (AUC=0.84) without worsening the FN rate. Its clinical performance was applied in a narrative case report as an example. Conclusion- This study developed a machine model with 84% prediction accuracy, which is able to assist clinicians in decision making process and contribute to develop new analytics to improve care at high technology readiness levels.

2020 - Marked T cell activation, senescence, exhaustion and skewing towards TH17 in patients with Covid-19 pneumonia. [Articolo su rivista]
De Biasi, S; Meschiari, M; Gibellini, L; Bellinazzi, C; Borella, R; Fidanza, L; Gozzi, L; Iannone, A; Lo Tartaro, D; Mattioli, M; Paolini, A; Menozzi, M; Milić, J; Franceschi, G; Fantini, R; Tonelli, R; Sita, M; Sarti, M; Trenti, T; Brugioni, L; Cicchetti, L; Facchinetti, F; Pietrangelo, A; Clini, E; Girardis, M; Guaraldi, G; Mussini, C; Cossarizza, A.
abstract

We provide an in-depth investigation of the T cell compartment and functionality, cytokine production and plasma levels in a total of 39 patients affected by Covid-19 pneumonia. At admission, patients were lymphopenic; for all, SARS-CoV-2 was detected in a nasopharyngeal swab specimen by real-time RT-PCR, and pneumonia was subsequently confirmed by X-rays. Detailed 18-parameter flow cytometry coupled with unsupervised data analysis revealed that patients showed similar percentages of CD4+ and CD8+ T cells, but a decreased absolute number in both populations. For CD4+ T lymphocytes, we found a significant decrease in the number of naïve, central and effector memory cells and an increased percentage of terminally differentiated cells, regulatory T cells, and of those that were activated or that were expressing PD1 and CD57 markers. Studies on chemokine receptors and lineage-specifying transcription factors revealed that, among CD4+ T cells, patients displayed a lower percentage of cells expressing CCR6 or CXCR3, and of those co-expressing CCR6 and CD161, but higher percentages of 62 CXCR4+ or CCR4+ cells. No differences were noted in the expression of T-bet or GATA-3. Analyses of patients' CD8+ T cells showed decreased numbers of naïve and central memory and increased amounts of activated cells, accompanied by increased percentages of activated cells and of lymphocytes expressing CD57, PD1, or both. CD8+ T cells expressed lower percentages of CCR6+, CXCR3+ or T-bet+ cells and of CXCR3+,T-bet+ or CCR6+,CD161+ lymphocytes. We also found higher percentages of cells expressing CCR4+, CXCR4 or GATA-3. Analyses of lymphocyte proliferation revealed that terminally differentiated CD4+ and CD8+ T cell from patients had a lower proliferative index than controls, whereas cellular bioenergetics, measured by the quantification of mitochondrial oxygen consumption and extracellular acidification rate, was similar in CD4+ T cells from both groups. We measured plasma level of 31 cytokines linked to inflammation, including T helper (TH)type-1 and TH2 cytokines, chemokines, galectins, pro- and anti-inflammatory mediators, finding that most were dramatically increased in Covid-19 patients, confirming the presence of a massive cytokine storm. Analysis of the production of different cytokines after stimulation by anti-CD3/CD28 monoclonal antibodies revealed that patients not only had a high capacity to produce tumour necrosis factor (TNF)-α, interferon (IFN)-γ and interleukin (IL)-2, but also showed a significant skewing of CD4+ T cells towards the TH17 phenotype. A therapeutic approach now exists based on the administration of drugs that block IL-6pathway, and seems to improve the disease. IL-17 is crucial in recruiting and activating neutrophils, cells that can migrate to the lung and are heavily involved in the pathogenesis of Covid-19. We show here that a skewing of activated T cells towards the TH17 functional phenotype exists in Covid-19 patients. We therefore suggest that blocking the IL-17 pathway by biological drugs that are already used to treat different pathologies could provide a novel, additional strategy to improve the health of patients infected by SARS-CoV-2.

2020 - New Drugs for NASH and HIV Infection: Great Expectations for a Great Need [Articolo su rivista]
Guaraldi, G.; Maurice, J. B.; Marzolini, C.; Monteith, K.; Milic, J.; Tsochatzis, E.; Bhagani, S.; Morse, C. G.; Price, J. C.; Ingiliz, P.; Lemoine, M.; Sebastiani, G.
abstract

In recent years, there has been an increasing number of clinical trials for the treatment of nonalcoholic steatohepatitis (NASH). People living with human immunodeficiency virus (PLWH) are commonly excluded from these studies, usually due to concerns over drug-drug interactions associated with antiretroviral therapy. The Steatohepatitis in HIV Emerging Research Network, a group of international experts in hepatology and infectious diseases, discusses our current understanding on the interaction between human immunodeficiency virus and NASH, and the issues related to the inclusion of PLWH in NASH clinical trials. Recent trials addressing NASH treatment in PLWH are discussed. The risk of drug-drug interactions between antiretroviral therapy and aramchol, cenicriviroc, elafibranor, obeticholic acid and resmetirom (MGL-3196), which are currently in phase 3 trials for the treatment of NASH, are reviewed. A model for trial design to include PLWH is proposed, strongly advocating for the scientific community to include this group as a subpopulation within studies.

2020 - Non-alcoholic fatty liver disease predicts development of metabolic comorbidities in HIV-infected patients [Articolo su rivista]
T, Krahn; M, Martel; R, Sapir-Pichhadze; N, Kronfli; Falutz, J; Guaraldi, G; Lebouche, B; M B, Klein; P, Wong; M, Deschenes; P, Ghali; G, Sebastiani
abstract

Cardiovascular and liver disease are main contributors to mortality in people with HIV (PWH). In HIV-uninfected patients, non-alcoholic fatty liver disease (NAFLD) is associated with incident metabolic complications. We investigated the effect of NAFLD on development of metabolic comorbidities in PWH.

2020 - Nosocomial COVID-19 infection: examining the risk of mortality. The COPE-Nosocomial Study (COVID in Older PEople) [Articolo su rivista]
Carter, B.; Collins, J. T.; Barlow-Pay, F.; Rickard, F.; Bruce, E.; Verduri, A.; Quinn, T. J.; Mitchell, E.; Price, A.; Vilches-Moraga, A.; Stechman, M. J.; Short, R.; Einarsson, A.; Braude, P.; Moug, S.; Myint, P. K.; Hewitt, J.; Pearce, L.; Mccarthy, K.; Davey, C.; Jones, S.; Lunstone, K.; Cavenagh, A.; Silver, C.; Telford, T.; Simmons, R.; Holloway, M.; Hesford, J.; El Jichi Mutasem, T.; Singh, S.; Paxton, D.; Harris, W.; Galbraith, N.; Bhatti, E.; Edwards, J.; Duffy, S.; Kelly, J.; Murphy, C.; Bisset, C.; Alexander, R.; Garcia, M.; Sangani, S.; Kneen, T.; Lee, T.; Mcgovern, A.; Guaraldi, G.; Clini, E.
abstract

Background: Hospital admissions for non-coronavirus disease 2019 (COVID-19) pathology have decreased significantly. It is believed that this may be due to public anxiety about acquiring COVID-19 infection in hospital and the subsequent risk of mortality. Aim: To identify patients who acquire COVID-19 in hospital (nosocomial COVID-19 infection (NC)) and their risk of mortality compared to those with community-acquired COVID-19 (CAC) infection. Methods: The COPE-Nosocomial Study was an observational cohort study. The primary outcome was the time to all-cause mortality (estimated with an adjusted hazard ratio (aHR)), and secondary outcomes were day 7 mortality and the time-to-discharge. A mixed-effects multivariable Cox's proportional hazards model was used, adjusted for demographics and comorbidities. Findings: The study included 1564 patients from 10 hospital sites throughout the UK, and one in Italy, and collected outcomes on patients admitted up to April 28th, 2020. In all, 12.5% of COVID-19 infections were acquired in hospital; 425 (27.2%) patients with COVID died. The median survival time in NC patients was 14 days compared with 10 days in CAC patients. In the primary analysis, NC infection was associated with lower mortality rate (aHR: 0.71; 95% confidence interval (CI): 0.51–0.98). Secondary outcomes found no difference in day 7 mortality (adjusted odds ratio: 0.79; 95% CI: 0.47–1.31), but NC patients required longer time in hospital during convalescence (aHR: 0.49, 95% CI: 0.37–0.66). Conclusion: The minority of COVID-19 cases were the result of NC transmission. No COVID-19 infection comes without risk, but patients with NC had a lower risk of mortality compared to CAC infection; however, caution should be taken when interpreting this finding.

2020 - Peritoneal dialysis in the time of coronavirus disease 2019 [Articolo su rivista]
Alfano, Gaetano; Fontana, Francesco; Ferrari, Annachiara; Guaraldi, Giovanni; Mussini, Cristina; Magistroni, Riccardo; Cappelli, Gianni; Bacca, Erica; Bedini, Andrea; Borghi, Vanni; Burastero, Giulia; Carli, Federica; Ciusa, Giacomo; Corradi, Luca; Cuomo, Gianluca; Digaetano, Margherita; Dolci, Giovanni; Faltoni, Matteo; Fantini, Riccardo; Franceschi, Giacomo; Franceschini, Ericad; Iadisernia, Vittorio; Larnõ, Damiano; Menozzi, Marianna; Meschiari, Marianna; Milic, Jovana; Orlando, Gabriella; Pellegrino, Francesco; Raimondi, Alessandro; Rogati, Carlotta; Santoro, Antonella; Tonelli, Roberto; Tutone, Marco; Volpi, Sara; Yaacoub, Dina; Aten, G.; Marco, Ballestri; Mori, Giacomo; Girardis, Massimo; Andreotti, Alberto; Biagioni, Emanuela; Bondi, Filippo; Busani, Stefano; Chierego, Giovanni; Scotti, Marzia; Serio, Lucia; Cossarizza, Andrea; Bellinazzi, Caterina; Borella, Rebecca; de Biasi, Sara; de Gaetano, Anna; Fidanza, Lucia; Gibellini, Lara; Iannone, Anna; Lo Tartaro, Domenico; Mattioli, Marco; Nasi, Milena; Paolini, Annamariag; Pinti, Marcello
abstract

In the current setting of global containment, peritoneal dialysis (PD) and home haemodialysis are the best modalities of renal replacement therapy (RRT) to reduce the rate of transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Considering the shorter and easier training programme of PD compared to home haemodialysis, PD appears a practical solution for patients with end-stage renal disease to reduce the risk of hospital-acquired infection. PD offers the advantage of minimizing the risk of viral transmission through interpersonal contact that commonly occurs during the haemodialysis session and while travelling from home to the haemodialysis facility using public transport services. To overcome barriers to health care access due to the containment measures for this emerging disease, telemedicine is a useful and reliable tool for delivering health care without exposing patients to the risk of contact. However, novel issues including handling of potentially infected dialysate, caregivers' infectious risk and adequacy of PD in critically ill patients with acute respiratory distress syndrome remain to be clarified. In conclusion, PD should be preferred to the other modalities of RRT during the coronavirus disease 2019 (COVID-19) outbreak because it can be a solution to cope with the increased number of infected patients worldwide.

2020 - Predicting Respiratory Failure in Patients with COVID-19 pneumonia: a case study from Northern Italy [Relazione in Atti di Convegno]
Ferrari, Davide; Mandreoli, Federica; Guaraldi, Giovanni; Milić, Jovana; Missier, Paolo
abstract

The Covid-19 crisis caught health care services around the world by surprise, putting unprecedented pressure on Intensive Care Units (ICU). To help clinical staff to manage the limited ICU capacity, we have developed a Machine Learning model to estimate the probability that a patient admitted to hospital with COVID-19 symptoms would develop severe respiratory failure and require Intensive Care within 48 hours of admission. The model was trained on an initial cohort of 198 patients admitted to the Infectious Disease ward of Modena University Hospital, in Italy, at the peak of the epidemic, and subsequently refined as more patients were admitted. Using the LightGBM Decision Tree ensemble approach, we were able to achieve good accuracy (AUC = 0.84) despite a high rate of missing values. Furthermore, we have been able to provide clinicians with explanations in the form of personalised ranked lists of features for each prediction, using only 20 out of more than 90 variables, using Shapley values to describe the importance of each feature.

2020 - Prediction of Esophageal Varices by Liver Stiffness and Platelets in Persons with HIV infection and Compensated Advanced Chronic Liver Disease [Articolo su rivista]
Merchante, Nicolas; Saroli Palumbo, Chiara; Mazzola, Giovanni; Pineda, Juan A; Téllez, Francisco; Rivero-Juárez, Antonio; Ríos-Villegas, Maria José; Maurice, James B; Westbrook, Rachel H; Judge, Rebekah; Guaraldi, Giovanni; Schepis, Filippo; Perazzo, Hugo; Rockstroh, Juergen; Boesecke, Christoph; Klein, Marina B; Cervo, Adriana; Ghali, Peter; Wong, Philip; Petta, Salvatore; De Ledinghen, Victor; Macías, Juan; Sebastiani, Giada
abstract

Human immunodeficiency virus (HIV)-infected individuals are at increased risk of cirrhosis and esophageal varices. Baveno VI criteria, based on liver stiffness measurement (LSM) and platelet count, have been proposed to avoid unnecessary esophagogastroduodenoscopy (EGD) screening for esophageal varices needing treatment (EVNT). This approach has not been validated in HIV-infected patients.

2020 - Pregnancy and neonatal outcomes in women with HIV-1 exposed to integrase inhibitors, protease inhibitors and non-nucleoside reverse transcriptase inhibitors: an observational study [Articolo su rivista]
Floridia, M.; Dalzero, S.; Giacomet, V.; Tamburrini, E.; Masuelli, G.; Savasi, V.; Spinillo, A.; Tassis, B.; Franceschetti, L.; Degli Antoni, A. M.; Sansone, M.; Guaraldi, G.; Vimercati, A.; Meloni, A.; Ravizza, M.
abstract

Purpose: Recommended regimens for pregnant women with HIV-1 are composed of two nucleoside reverse transcriptase inhibitors (NRTI) plus either a ritonavir-boosted protease inhibitor (PI) or an integrase strand transfer inhibitor (ISTI), with non-nucleoside reverse transcriptase inhibitors (NNRTI) representing an alternative drug class. The study’s purpose was to compare these three options in terms of pregnancy outcomes. Methods: Data from a national observational study of pregnant women with HIV-1 were used. The analysis included all pregnancies reported between 2008 and 2018, ending in live births and exposed within 32 weeks of gestation to three-drug regimens composed of a NRTI backbone plus a PI, a NNRTI or a ISTI, without class switching during pregnancy. Clinical and laboratory outcomes were evaluated in univariate and multivariable analyses. Results: Overall, 794 exposed pregnancies were analyzed (PI 78.4%, NNRTI 15.4%, ISTI 6.2%). Almost all outcomes had similar rates in the three groups. Women who received PI in pregnancy were less likely to be virologically suppressed at third trimester. PI use was associated with higher bilirubin and triglyceride levels, and ISTI use with a lower rate of low birthweight. The differences in viral suppression at third trimester and in low birthweight were not maintained in multivariable analyses that were adjusted for confounders. Discussion: We found no major differences in a wide range of outcomes relevant for pregnant women with HIV. Such results are reassuring, and this information may be helpful in a context of preconception counseling when therapeutic choices for pregnancy are discussed between women and care providers.

2020 - Prevalence, Correlates and Outcomes of Smoking in Pregnant Women with HIV: A National Observational Study in Italy [Articolo su rivista]
Floridia, M.; Ravizza, M.; Masuelli, G.; Tassis, B.; Savasi, V. M.; Liuzzi, G.; Sansone, M.; Simonazzi, G.; Franceschetti, L.; Meloni, A.; Vimercati, A.; Guaraldi, G.; Pinnetti, C.; Dalzero, S.; Tamburrini, E.
abstract

Background: Few studies have evaluated in pregnant women with HIV the prevalence of smoking and its associations with maternal and neonatal outcomes. Objectives: to assess the prevalence of smoking among women with HIV in early pregnancy and the association between smoking and pregnancy outcomes in this particular population. Methods: We used data from a multicenter observational study to define the prevalence of smoking in women with HIV in early pregnancy, and the role of smoking status and intensity as risk factors for adverse maternal and neonatal outcomes. Main outcome measures were fetal growth restriction [FGR], preterm delivery [PD] and low birthweight [LB], evaluated in univariate and multivariate analyses. Results: The overall (2001–2018) prevalence of reported smoking (at least one cigarette/day) was 25.6% (792/3097), with a significant decrease in recent years (19.0% in 2013–2018). Women who smoked were less commonly African, had lower body mass index, older age, a longer history of HIV infection and higher CD4 counts. In univariate analyses, smokers were significantly more likely to have PD, LB, FGR and detectable HIV viral load at third trimester. Multivariable analyses confirmed for smokers a significantly higher risk of LB (adjusted odds ratio [AOR]: 1.69, 95%CI 1.22–2.34) and FGR (AOR 1.88, 95%CI 1.27–2.80), while the associations with detectable HIV and PD were not maintained. Conclusions: The common prevalence of smoking among pregnant women with HIV and its association with adverse outcomes indicates that smoking cessation programs in this population may have a significant impact on neonatal and maternal health.

2020 - Prevalence, Predictors, and Severity of Lean Nonalcoholic Fatty Liver Disease in Patients Living With Human Immunodeficiency Virus [Articolo su rivista]
Cervo, Adriana; Milic, Jovana; Mazzola, Giovanni; Schepis, Filippo; Petta, Salvatore; Krahn, Thomas; Lebouche, Bertrand; Deschenes, Marc; Cascio, Antonio; Guaraldi, Giovanni; Sebastiani, Giada
abstract

The burden of non-alcoholic fatty liver disease (NAFLD) is growing in people with HIV. NAFLD is associated with obesity, however it can occur in normoweight (lean) patients. We aimed to investigate lean NAFLD in HIV-infected patients.

2020 - RAAS inhibitors are not associated with mortality in COVID-19 patients: findings from an observational multicenter study in Italy and a meta-analysis of 19 studies [Articolo su rivista]
Di Castelnuovo, Augusto; Costanzo, Simona; Antinori, Andrea; Berselli, Nausicaa; Blandi, Lorenzo; Bonaccio, Marialaura; Cauda, Roberto; Gialluisi, Alessandro; Guaraldi, Giovanni; Menicanti, Lorenzo; Mennuni, Marco; Mussinelli, Roberta; My, Ilaria; Parruti, Giustino; Patti, Giuseppe; Perlini, Stefano; Santilli, Francesca; Signorelli, Carlo; Stefanini, Giulio G; Vergori, Alessandra; Abete, Paolo; Ageno, Walter; Agostoni, Piergiuseppe; Aiello, Luca; Al Moghazi, Samir; Arboretti, Rosa; Aucella, Filippo; Barbieri, Greta; Barchitta, Martina; Bartoloni, Alessandro; Bonfanti, Paolo; Cacciatore, Francesco; Caiano, Lucia; Carrozzi, Laura; Cascio, Antonio; Castiglione, Giacomo; Cianfrone, Stefania; Ciccullo, Arturo; Cingolani, Antonella; Cipollone, Francesco; Colomba, Claudia; Colombo, Crizia; Cozzi, Ottavia; Crisetti, Annalisa; Crosta, Francesca; Danzi, Gian Battista; D'Ardes, Damiano; de Gaetano Donati, Katleen; Di Gennaro, Francesco; Di Tano, Giuseppe; D'Offizi, Gianpiero; Fusco, Francesco Maria; Gentile, Ivan; Graziani, Emauele; Guarnieri, Gabriella; Larizza, Giovanni; Leone, Armando; Lio, Veronica; Lucia, Mothanje Barbara; Maccagni, Gloria; Madaro, Ferruccio; Maitan, Stefano; Mancarella, Sandro; Manuele, Rosa; Mapelli, Massimo; Maragna, Riccardo; Marcucci, Rossella; Maresca, Giulio; Marongiu, Silvia; Marotta, Claudia; Marra, Lorenzo; Mastroianni, Franco; Mazzitelli, Maria; Mengozzi, Alessandro; Menichetti, Francesco; Meschiari, Marianna; Milic, Jovana; Minutolo, Filippo; Molena, Beatrice; Mussini, Cristina; Musso, Maria; Odone, Anna; Olivieri, Marco; Palimodde, Antonella; Pasi, Emanuela; Pesavento, Raffaele; Petri, Francesco; Pinchera, Biagio; Pivato, Carlo A; Poletti, Venerino; Ravaglia, Claudia; Rossato, Marco; Rossi, Marianna; Sabena, Anna; Salinaro, Francesco; Sangiovanni, Vincenzo; Sanrocco, Carlo; Scoppettuolo, Giancarlo; Scorzolini, Laura; Sgariglia, Raffaella; Simeone, Paola Giustina; Trecarichi, Enrico Maria; Vettor, Roberto; Vianello, Andrea; Vinceti, Marco; Virano, Alexandra; Vocciante, Laura; Iacoviello, Licia; Caterina, Null
abstract

OBJECTIVE: The hypothesis that been set forward that use of Renin Angiotensin Aldosterone System (RAAS) inhibitors is associated with COVID-19 severity. We set-up a multicenter Italian collaboration (CORIST Project, ClinicalTrials.gov ID: NCT04318418) to retrospectively investigate the relationship between RAAS inhibitors and COVID-19 in-hospital mortality. We also carried out an updated meta-analysis on the relevant studies.METHODS: We analyzed 4,069 unselected patients with laboratory-confirmed SARS-CoV-2 infection and hospitalized in 34 clinical centers in Italy from February 19, 2020 to May 23, 2020. The primary end-point in a time-to event analysis was in-hospital death, comparing patients who received angiotensin-converting-enzyme inhibitors (ACE-I) or angiotensin-receptor blockers (ARB) with patients who did not. Articles for the meta-analysis were retrieved until July 13th, 2020 by searching in web-based libraries, and data were combined using the general variance-based method.RESULTS: Out of 4,069 COVID-19 patients, 13.5% and 13.3% received ACE-I or ARB, respectively. Use of neither ACE-I nor ARB was associated with mortality (multivariable hazard ratio (HR) adjusted also for COVID-19 treatments: 0.96, 95% confidence interval 0.77-1.20 and HR=0.89, 0.67-1.19 for ACE-I and ARB, respectively). Findings were similar restricting the analysis to hypertensive (N=2,057) patients (HR=1.00, 0.78-1.26 and HR=0.88, 0.65-1.20) or when ACE-I or ARB were considered as a single group. Results from the meta-analysis (19 studies, 29,057 COVID-19 adult patients, 9,700 with hypertension) confirmed the absence of association.CONCLUSIONS: In this observational study and meta-analysis of the literature, ACE-I or ARB use was not associated with severity or in-hospital mortality in COVID-19 patients.

2020 - Rituximab in people living with HIV affected by immune-mediated renal diseases: a case-series [Articolo su rivista]
Alfano, G.; Giaroni, F.; Fontana, F.; Neri, L.; Mosconi, G.; Mussini, C.; Guaraldi, G.; Cappelli, G.
abstract

Over the last two decades, rituximab (RTX) has played an important role in the treatment of some lymphoproliferative malignancies and immune-mediated diseases. RTX administration is generally safe and well-tolerated, but side effects including late-onset neutropenia, hypogammaglobulinemia, hepatitis B reactivation and rare cases of progressive multifocal leukoencephalopathy have been observed after its administration. Although there are no absolute contraindications regarding its use in people living with HIV (PLWH), the prescription of this drug has been principally limited in patients with oncohematological diseases. In this report, we described the outcome of four PLWH who underwent RTX therapy after the diagnosis of immune-mediated renal disease. The main RTX-associated adverse effects were leukopenia, late-onset neutropenia and decline of CD4+ and CD8+ T-cell counts. In addition, two of the four patients experienced pneumonia requiring hospitalization within six months from the last RTX infusion. We suggest that RTX should be used with caution in PLWH until further evidence emerges on its safety profile in this vulnerable population.

2020 - Role of Maraviroc in minimizing the risk of graft rejection in HIV-infected kidney transplant recipients [Articolo su rivista]
Alfano, Gaetano; Guaraldi, Giovanni; Fontana, Francesco; Franceschini, Erica; Dolci, Giovanni; Mussini, Cristina; Cappelli, Gianni
abstract

Background Kidney transplantation in HIV-infected patients is characterized by a concerning high rate of allograft rejections. The etiological mechanisms leading to this increased immunoreactivity are still unknown. Maraviroc is a new antiretroviral agent that has been associated with immunomodulatory proprieties; therefore, its use may be a promising strategy to minimize the rate of rejections in HIV-infected kidney transplant (KT) recipients.Methods We conducted a retrospective study in our cohort of HIV-KT recipients with the aim to explore the effects of maraviroc in reducing the risk of graft rejection.Results Twenty-two HIV-infected KT recipients predominantly of Caucasian origin (86%) and with a median age of 49 (IQR, 51.9-42.2) years were evaluated. Ten HIV-infected patients were treated with maraviroc and 12 with a maraviroc-free antiretroviral regimen. After a median follow-up of 3.01 years, half of the maraviroc-treated patients (n = 5) developed seven episodes of graft rejection, most of them were T cell-mediated rejections (85.7%). Five episodes were recorded in the maraviroc-free group. The difference in the rate of graft rejections was not statistically significant (P = .23).Conclusions The administration of maraviroc was ineffective in preventing graft rejections in our cohort of patients.

2020 - SARS-CoV-2, the Virus that Causes COVID-19: Cytometry and the New Challenge for Global Health [Articolo su rivista]
Cossarizza, A.; De Biasi, S.; Guaraldi, G.; Girardis, M.; Mussini, C.
abstract

2020 - Sex Differences in People Aging With HIV [Articolo su rivista]
Brañas, Fátima; Sánchez-Conde, Matilde; Carli, Federica; Menozzi, Marianna; Raimondi, Alessandro; Milic, Jovana; Franconi, Jacopo; Cuomo, Gianluca; Mussini, Cristina; Moreno, Santiago; Guaraldi, Giovanni
abstract

To evaluate differences between older women and men with HIV regarding HIV variables, comorbidity, physical function, and quality of life (QOL).

2020 - Successful treatment of BK virus associated-nephropathy in a human immunodeficiency virus-positive kidney transplant recipient [Articolo su rivista]
Alfano, Gaetano; Fontana, Francesco; Guaraldi, Giovanni; Cappelli, Gianni; Mussini, Cristina
abstract

BK virus (BKV) is an opportunistic pathogen in those with impaired immunity. Viral replication is generally asymptomatic but is able to induce cytopathic alterations in renal cells. If BKV infection is left untreated, it leads to BKV-associated nephropathy (BKVAN) and graft loss. There is scarce experience in the management of BKV infection in kidney transplant recipients living with HIV. We report the successful treatment of BKVAN in an HIV-positive kidney transplant recipient who experienced BKV replication in the immediate post-transplantation period. A change in therapy from calcineurin inhibitor to sirolimus, steroid withdrawal and a short course of an immunomodulatory agent (leflunomide) controlled BKV viremia in the absence of drug side-effects or impairment of graft function.

2020 - Surfactant replacement might help recovery of low-compliance lung in severe COVID-19 pneumonia. [Articolo su rivista]
Busani, S; Dall’Ara, L; Tonelli, R; Clini, E; Munari, E; Venturelli, S; Meschiari, M; Guaraldi, G; Cossarizza, A; Ranieri, Mv; Girardis, M.
abstract

It has been hypothesized that there is a reduced AT2 cells number with low ability to synthesize and secrete endogenous surfactant in COVID-19 patients. To our knowledge, exogenous surfactant replacement has not been described so far in COVID-19 patients. We here report five cases of critically ill COVID-19 undergoing exogenous surfactant instillation through the airways.

2020 - Switching from boosted PIs to dolutegravir in HIV-infected patients with high cardiovascular risk: 48 week effects on subclinical cardiovascular disease [Articolo su rivista]
Gonzalez-Cordon, Ana; Assoumou, Lambert; Camafort, Miguel; Domenech, Monica; Guaraldi, Giovanni; Domingo, Pere; Rusconi, Stefano; Raffi, François; Katlama, Christine; Masia, Mar; I Bernardino, Jose; Saumoy, Maria; Pozniak, Anton; M Gatell, Jose; Martinez, Esteban
abstract

2020 - Testicular pain as an unusual presentation of COVID-19: a brief review of SARS-CoV-2 and the testis [Articolo su rivista]
La Marca, Antonio; Busani, Stefano; Donno, Valeria; Guaraldi, Giovanni; Ligabue, Guido; Girardis, Massimo
abstract

Can the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus induce testis damage and dysfunction?

2020 - Testosterone (T) is poorly related to sexual desire and Erectile Dysfunction (ED) in Young/Middle Aged Human immunodeficiency virus (HIV)-Infected Men [Abstract in Atti di Convegno]
De Vincentis, S.; Decaroli, M. C.; Diazzi, C; Morini, F.; Bertani, D.; Fanelli, F.; Mezzullo, M.; Santi, D.; Tartaro, G.; Baraldi, E.; Tagliavini, S.; Pagotto, U.; Guaraldi, G.; Rochira, V.
abstract

Background ED is highly prevalent in HIV-infected men. T leads sexual behavior in men, but preliminary data suggests that ED is poorly related to serum T in HIV- infected men. Aim To explore the relationship between sexual function and gonadal function in young/middle-aged HIV-infected men. Methodology Prospective, cross-sectional, observational study on HIV-infected men (age <50 years). Serum TT was assessed by the gold standard LC-MS/MS. Sex hormone-binding globulin (SHBG) was measured by chemiluminescent im- munoassay and calculated free T (cFT) was obtained by Vermeulen equa- tion. Biochemical hypogonadism was defined as TT levels below 320ng/ dl and/or cFT levels below 64pg/ml. The validated International Index of Erectile Function (IIEF)-15 questionnaire was used to identify the presence of ED (score <25) and its degree. IIEF-5 was performed to check if it is reliable as IIEF-15 in this setting. Statistical analysis Continuous and categorical variables were compared using ANOVA univari- ate and Chi-Square test. Correlations were performed using linear regression models.Results 315 consecutive HIV-infected men were enrolled (mean age 45.3 ± 5.3 years; mean duration of HIV-infection 16.3 ± 8.8 years). A total of 187 patients (59.7%) had ED at IIEF-15; 59 patients (31.5%) presented a severe form of ED (score <10). Considering gonadal function, 35 patients (11.1%) had T deficiency. Scores of EF (P=0.039) and sexual desire (P=0.015) domains were higher in hypogonadal than eugonadal men. Accordingly, the prev- alence of ED raised to 71.4% among hypogonadal men. By considering ED severity, patients with severe ED showed a longer duration of infection (P = 0.039) and lower cFT levels (P = 0.041) than patients with mild ED. No difference was found for age (P = 0.224) and TT levels (P = 0.110). IIEF-15 score was inversely related to duration of infection (R2 = 0.030, beta = –0.173, P = 0.002) and patients’ age (R2 = 0.020, beta = –0.140, P = 0.013).No signif- icant correlation was found between IIEF-15 score and total T (P = 0.236) and cFT (P = 0.126). The erectile function domain at IIEF-15 directly cor- related with IIEF-5 score (R2 = 0.545, beta = 0.778, P < 0.001). Conclusions In our HIV-cohort of young/middle-aged men, the prevalence of ED and T deficiency were high being of 60% and 11%, respectively. Serum TT and cFT did not correlate with sexual function parameters, even though sexual desire was lower in men with hypogonadism. ED seems to be better predict- ed by other factors, such as the duration of infection in this clinical setting, rather than the gonadal status. Furthermore, IIEF-5 seems to be as reliable as IIEF-15 for ED diagnosis in HIV-infected men

2020 - The EuroSIDA study: 25 years of scientific achievements [Articolo su rivista]
Laut, K; Kirk, O; Rockstroh, J; Phillips, A; Ledergerber, B; Gatell, J; Gazzard, B; Horban, A; Karpov, I; Losso, M; d'Arminio Monforte, A; Pedersen, C; Ristola, M; Reiss, P; Scherrer, A U; de Wit, S; Aho, I; Rasmussen, L D; Svedhem, V; Wandeler, G; Pradier, C; Chkhartishvili, N; Matulionyte, R; Oprea, C; Kowalska, J D; Begovac, J; Miró, J M; Guaraldi, G; Paredes, R; Raben, D; Podlekareva, D; Peters, L; Lundgren, J D; Mocroft, A
abstract

The EuroSIDA study was initiated in 1994 and follows adult people living with HIV (PLHIV) in 100 collaborating clinics across 35 countries covering all European regions, Israel and Argentina. The study aims to study the long-term virological, immunological and clinical outcomes of PLHIV and to monitor temporal changes and regional differences in outcomes across Europe. Annually collected data include basic demographic characteristics, information on AIDS- and non-AIDS-related clinical events, and details about antiretroviral therapy (ART), hepatitis C treatment and other medications, in addition to a range of laboratory values. The summer 2016 data set held data from a total of 23 071 individuals contributing 174 481 person-years of follow-up, while EuroSIDA's unique plasma repository held over 160 000 samples. Over the past 25 years, close to 300 articles have been published in peer-reviewed journals (h-index 52), covering a range of scientific focus areas, including monitoring of clinical and virological outcomes, ART uptake, efficacy and adverse events, the influence of hepatitis virus coinfection, variation in the quality of HIV care and management across settings and regions, and biomarker research. Recognizing that there remain unresolved issues in the clinical care and management of PLHIV in Europe, EuroSIDA was one of the cohorts to found The International Cohort Consortium of Infectious Disease (RESPOND) cohort consortium on infectious diseases in 2017. In celebration of the EuroSIDA study's 25th anniversary, this article aims to summarize key scientific findings and outline current and future scientific focus areas.

2020 - The Lisbon patient: Exceptional longevity with HIV suggests healthy aging as an ultimate goal for HIV care [Articolo su rivista]
Pintassilgo, I.; Cesari, M.; Santos, H. N.; Milic, J.; Franconi, I.; Mussini, C.; Marques, N.; Guaraldi, G.
abstract

In the context of global aging, HIV infection has become a new chronic disease and requires innovative models of care. Treating isolated comorbidities represents a useless and potentially harmful practice at advanced age. Therefore, a patient-centered approach, in which the interventions are focused on the biology and function of the individual, with understanding of the importance of securing social and home environment that provides psychosocial support, better suits unmet health needs. We present a paradigmatic case of healthy aging: the first reported HIV-infected patient who achieved 100th of life - the Lisbon patient. The construct of healthy aging, recently introduced by the World Health Organization, is the best example of this comprehensive model and could represent the fourth target of UNAIDS agenda of the end of AIDS.

2020 - The Role of the Renin-Angiotensin System in Severe Acute Respiratory Syndrome-CoV-2 Infection [Articolo su rivista]
Alfano, Gaetano; Guaraldi, Giovanni; Fontana, Francesco; Ferrari, Annachiara; Magistroni, Riccardo; Mussini, Cristina; Cappelli, Gianni
abstract

2020 - Therapeutic management of HIV-infected patients with chronic kidney disease [Articolo su rivista]
Alfano, Gaetano; Guaraldi, Giovanni; Fontana, Francesco; Bellasi, Antonio; Cappelli, Gianni
abstract

CKD and HIV infection are two chronic diseases impacting heavily on the survival of the affected patients. The interplay between HIV infection and chronic kidney disease (CKD) is complex and interactions occur at multiple levels. Approach to the management of HIV-infected patients requires special attention to face the numerous therapeutic difficulties ranging from drug-drug interactions to drug-toxicity. The most effective strategy is targeted to suppression of HIV viral load, as it dramatically changes the prognosis of the patients as well as prevents the development of HIV-associated kidney disease. As shown in this review, the approach to the therapeutic management of CKD in the setting of HIV infection varies in relation to the degree of renal impairment.

2020 - Tocilizumab for severe COVID-19 pneumonia – Authors' reply [Articolo su rivista]
Guaraldi, Giovanni; Meschiari, Marianna; Milic, Jovana; Cozzi-Lepri, Alessandro; Mussini, Cristina
abstract

2020 - Tocilizumab in COVID-19: finding the optimal route and dose – Authors' reply [Articolo su rivista]
Guaraldi, G.; Milic, J.; Cozzi-Lepri, A.; Pea, F.; Mussini, C.
abstract

2020 - Tocilizumab in patients with severe COVID-19: a retrospective cohort study [Articolo su rivista]
Guaraldi, G; Meschiari, M; Cozzi-Lepri, A; Milic, J; Tonelli, R; Menozzi, M; Franceschini, E; Cuomo, G; Orlando, G; Borghi, V; Santoro, A; Di Gaetano, M; Puzzolante, C; Carli, F; Bedini, A; Corradi, L; Fantini, R; Castaniere, I; Tabbì, L; Girardis, M; Tedeschi, S; Giannella, M; Bartoletti, M; Pascale, R; Dolci, G; Brugioni, L; Pietrangelo, A; Cossarizza, A; Pea, F; Clini, E; Salvarani, C; Massari, M; Viale, Pl; Mussini, C.
abstract

Background- There is no approved therapy for COVID-19 pneumonia. The aim of this multicentre cohort study was to assess the role of tocilizumab in reducing the risk of invasive mechanical ventilation and/or death in patients with severe COVID-19 pneumonia who received standard of care (SoC) treatment. Methods- The TESEO Cohort Study is a retrospective, multicentre observational cohort study of patients with COVID-19 severe pneumonia treated with SoC with or without tocilizumab using intravenous (IV) or subcutaneous (SC) formulations, identifying respectively treated and comparator groups. Survival analysis was performed with participants’ follow-up accruing from the date of entry into clinics until initiation of invasive mechanical ventilation or death, used as a composite outcome. Treatment groups were compared using Kaplan-Meier curves and Cox regression analysis after adjusting for gender, age and baseline Sequential Organ Failure Assessment (SOFA) score. Findings- Of 544 patients included, 179 patients were treated with tocilizumab: 88 with the IV (16.1%) and 91 with SC formulation (16.7%). Mortality was significantly higher in the comparator group (20%) as opposed to tocilizumab IV (6.8%) and tocilizumab SC (7.7%) (p<0.001). A reduced risk of invasive mechanical ventilation/death was shown for participants treated with tocilizumab from fitting a Cox regression analysis adjusted for gender, age and SOFA score (aHR=0.61, 95% CI:0.40-0.92; p=0.02). We found no evidence for a difference between IV and SC administration route of tocilizumab. With regards to the mortality endpoint alone, a reduced risk was observed comparing tocilizumab with the comparator group (aHR=0.38 95% CI:0.17-0.83, p=0.02) . Interpretation- Tocilizumab, regardless of IV or SC administration may be capable of reducing invasive mechanical ventilation or death in severe COVID-19 pneumonia. Our observations should be confirmed in randomised studies. Funding- This study was not funded.

2020 - Use of hydroxychloroquine in hospitalised COVID-19 patients is associated with reduced mortality: Findings from the observational multicentre Italian CORIST study [Articolo su rivista]
Castelnuovo, A. D.; Costanzo, S.; Antinori, A.; Berselli, N.; Blandi, L.; Bruno, R.; Cauda, R.; Guaraldi, G.; Menicanti, L.; My, I.; Parruti, G.; Patti, G.; Perlini, S.; Santilli, F.; Signorelli, C.; Spinoni, E.; Stefanini, G. G.; Vergori, A.; Ageno, W.; Agodi, A.; Aiello, L.; Agostoni, P.; Moghazi, S. A.; Astuto, M.; Aucella, F.; Barbieri, G.; Bartoloni, A.; Bonaccio, M.; Bonfanti, P.; Cacciatore, F.; Caiano, L.; Cannata, F.; Carrozzi, L.; Cascio, A.; Ciccullo, A.; Cingolani, A.; Cipollone, F.; Colomba, C.; Crosta, F.; Pra, C. D.; Danzi, G. B.; D'Ardes, D.; Donati, K. D. G.; Giacomo, P. D.; Gennaro, F. D.; Tano, G. D.; D'Offizi, G.; Filippini, T.; Fusco, F. M.; Gentile, I.; Gialluisi, A.; Gini, G.; Grandone, E.; Grisafi, L.; Guarnieri, G.; Lamonica, S.; Landi, F.; Leone, A.; Maccagni, G.; Maccarella, S.; Madaro, A.; Mapelli, M.; Maragna, R.; Marra, L.; Maresca, G.; Marotta, C.; Mastroianni, F.; Mazzitelli, M.; Mengozzi, A.; Menichetti, F.; Meschiari, M.; Minutolo, F.; Montineri, A.; Mussinelli, R.; Mussini, C.; Musso, M.; Odone, A.; Olivieri, M.; Pasi, E.; Petri, F.; Pinchera, B.; Pivato, C. A.; Poletti, V.; Ravaglia, C.; Rinaldi, M.; Rognoni, A.; Rossato, M.; Rossi, I.; Rossi, M.; Sabena, A.; Salinaro, F.; Sangiovanni, V.; Sanrocco, C.; Scorzolini, L.; Sgariglia, R.; Simeone, P. G.; Spinicci, M.; Trecarichi, E. M.; Venezia, A.; Veronesi, G.; Vettor, R.; Vianello, A.; Vinceti, M.; Vocciante, L.; De Caterina, R.; Iacoviello, L.
abstract

Background: Hydroxychloroquine (HCQ) was proposed as potential treatment for COVID-19. Objective: We set-up a multicenter Italian collaboration to investigate the relationship between HCQ therapy and COVID-19 in-hospital mortality. Methods: In a retrospective observational study, 3,451 unselected patients hospitalized in 33 clinical centers in Italy, from February 19, 2020 to May 23, 2020, with laboratory-confirmed SARS-CoV-2 infection, were analyzed. The primary end-point in a time-to event analysis was in-hospital death, comparing patients who received HCQ with patients who did not. We used multivariable Cox proportional-hazards regression models with inverse probability for treatment weighting by propensity scores, with the addition of subgroup analyses. Results: Out of 3,451 COVID-19 patients, 76.3% received HCQ. Death rates (per 1,000 person-days) for patients receiving or not HCQ were 8.9 and 15.7, respectively. After adjustment for propensity scores, we found 30% lower risk of death in patients receiving HCQ (HR=0.70; 95%CI: 0.59 to 0.84; E-value=1.67). Secondary analyses yielded similar results. The inverse association of HCQ with inpatient mortality was particularly evident in patients having elevated C-reactive protein at entry. Conclusions: HCQ use was associated with a 30% lower risk of death in COVID-19 hospitalized patients. Within the limits of an observational study and awaiting results from randomized controlled trials, these data do not discourage the use of HCQ in inpatients with COVID-19.

2020 - Virological response and retention in care according to time of starting ART in Italy: Data from the Icona Foundation Study cohort [Articolo su rivista]
D'Arminio Monforte, A.; Tavelli, A.; Cozzi-Lepri, A.; Castagna, A.; Passerini, S.; Francisci, D.; Saracino, A.; Maggiolo, F.; Lapadula, G.; Girardi, E.; Perno, C. F.; Antinori, A.; Andreoni, M.; Castelli, F.; Cauda, R.; Di Perri, G.; Galli, M.; Iardino, R.; Ippolito, G.; Lazzarin, A.; Marchetti, G. C.; Rezza, G.; Von Schloesser, F.; Viale, P.; Ceccherini-Silberstein, F.; Lo Caputo, S.; Mussini, C.; Puoti, M.; Bai, F.; Balotta, C.; Bandera, A.; Bonora, S.; Borderi, M.; Calcagno, A.; Capetti, A.; Capobianchi, M. R.; Cicalini, S.; Cingolani, A.; Cinque, P.; De Luca, A.; Di Biagio, A.; Gianotti, N.; Gori, A.; Guaraldi, G.; Lichtner, M.; Madeddu, G.; Monno, L.; Nozza, S.; Pinnetti, C.; Quiros Roldan, E.; Rossotti, R.; Rusconi, S.; Santoro, M. M.; Sarmati, L.; Fanti, I.; Galli, L.; Lorenzini, P.; Rodano, A.; Macchia, M.; Carletti, F.; Carrara, S.; Di Caro, A.; Graziano, S.; Petroni, F.; Prota, G.; Truffa, S.; Giacometti, A.; Costantini, A.; Barocci, V.; Angarano, G.; Milano, E.; Suardi, C.; Donati, V.; Verucchi, G.; Castelnuovo, F.; Minardi, C.; Menzaghi, B.; Abeli, C.; Cacopardo, B.; Celesia, B.; Vecchiet, J.; Falasca, K.; Pan, A.; Lorenzotti, S.; Sighinolfi, L.; Segala, D.; Blanc, P.; Vichi, F.; Cassola, G.; Viscoli, C.; Alessandrini, A.; Bobbio, N.; Mazzarello, G.; Fondaco, L.; Bonfanti, P.; Molteni, C.; Chiodera, A.; Milini, P.; Nunnari, G.; Pellicano, G.; Rizzardini, G.; Cannizzo, E. S.; Moioli, M. C.; Piolini, R.; Bernacchia, D.; Salpietro, S.; Tincati, C.; Puzzolante, C.; Migliorino, C.; Sangiovanni, V.; Borgia, G.; Esposito, V.; Di Flumeri, G.; Gentile, I.; Rizzo, V.; Cattelan, A. M.; Marinello, S.; Cascio, A.; Trizzino, M.; Schiaroli, E.; Parruti, G.; Sozio, F.; Magnani, G.; Ursitti, M. A.; Cristaudo, A.; Vullo, V.; Acinapura, R.; Moschese, D.; Capozzi, M.; Mondi, A.; Rivano Capparuccia, M.; Iaiani, G.; Latini, A.; Gagliardini, R.; Plazzi, M. M.; De Girolamo, G.; Vergori, A.; Cecchetto, M.; Viviani, F.; De Vito, A.; Rossetti, B.; Montagnani, F.; Franco, A.; Fontana Del Vecchio, R.; Di Giuli, C.; Caramello, P.; Orofino, G. C.; Sciandra, M.; Bassetti, M.; Londero, A.; Manfrin, V.; Battagin, G.; Starnini, G.; Ialungo, A.
abstract

Objectives: To describe: (i) factors associated with rapid and delayed ART initiation; (ii) rates of 12 week virological response; and (iii) virologically controlled retention in care by 1 year from ART initiation according to timing of start in a real-life setting. Methods: All individuals in the Icona cohort diagnosed with HIV in 2016-17 who initiated ART were grouped according to the time between HIV diagnosis and ART initiation: Group 1, ≤7 days; Group 2, 8-14 days; Group 3, 15-30 days; Group 4, 31-120 days; and Group 5, >120 days. Multivariable logistic regression models were used to identify factors associated with: (i) the probability of rapid (Group 1) and very delayed (Group 5) ART initiation; (ii) the 12 week virological response (by a modified snapshot algorithm); and (iii) the probability of retention in care at 1 year (on ART with HIV-RNA <50 copies/mL). Results: A total of 1247 individuals were included [82 (6.6%) in Group 1, 115 (9.2%) in Group 2, 267 (21.4%) in Group 3, 641 (51.4%) in Group 4 and 142 (11.4%) in Group 5]. Main predictors of rapid ART start (Group 1) were low CD4 cell count and high HIV-RNA at first contact with the infectious diseases centre. There was no association between probability of virological response and timing of ART initiation. Overall, 90% of individuals remained on ART after 1 year, 91% with undetectable HIV-RNA. Participants of Italian nationality, those with higher CD4 cell count and lower HIV-RNA at ART initiation were more likely to be retained in care after 1 year. Conclusions: In our high-income observational setting, we did not observe differences in the 1 year rate of virological response and retention in care according to timing of ART initiation.

2020 - Vitamin e as a 'bridge' therapy for nonalcoholic steatohepatits in HIV: What is waiting on the other side of the bridge? [Articolo su rivista]
Guaraldi, G.; Milic, J.
abstract

2020 - Why am I getting fat? Exploring immune-metabolic pathways to central fat accumulation in persons with HIV [Articolo su rivista]
Guaraldi, G; Milic, J
abstract

2020 - 18Fluoride-based molecular imaging of coronary atherosclerosis in HIV infected patients [Articolo su rivista]
Guaraldi, G.; Milic, J.; Prandini, N.; Ligabue, G.; Esposito, F.; Ciusa, G.; Malagoli, A.; Scaglioni, R.; Besutti, G.; Beghetto, B.; Nardini, G.; Roncaglia, E.; Mussini, C.; Raggi, P.
abstract

Background and aims: Molecular imaging with 18Fluorodeoxyglucose (FDG) and 18F-sodium-fluoride (NaF) captures arterial inflammation and micro-calcification and can reveal potentially unstable atherosclerotic plaques. Methods: We performed FDG and NaF PET/CT imaging in two clinically similar cohorts of patients living with HIV (PLWH) with no symptomatic cardiovascular disease. The prevalence and intensity of coronary artery uptake of each tracer, measured as target-to-background ratio (TBR), were assessed in patients at low and high cardiovascular risk. Results: Ninety-three PLWH were submitted to PET/CT imaging with FDG (N = 43) and NaF (N = 50); 42% were at low and 58% at high cardiovascular risk. The intensity of uptake and multivessel coronary artery uptake were significantly higher with NaF than FDG both in low and high-risk patients. When each 18F-tracer was tested in low and high-risk patients, an equal proportion of subjects showed no vessel, single and multivessel NaF uptake; the same was true for no and single vessel uptake of FDG (no multivessel FDG uptake was noted). Waist circumference, CRP, D-dimer, HIV duration and treatment with nucleoside reverse transcriptase inhibitors were associated with high NaF uptake in univariable analyses; D-dimer remained significant in multivariable analyses (OR = 1.05; p=0.02). There were no significant associations with FDG uptake. Conclusions: The prevalence of coronary artery uptake was higher with NaF compared to FDG both in high and low risk patients, hence microcalcification imaging may be a more sensitive tool to detect coronary atherosclerosis than inflammation imaging. However, the uptake of each 18Fluoride tracer was similar between low and high-risk subjects, and this underscores the discordance between clinical and imaging based risk assessment. Future investigation should address the prognostic significance of NaF coronary artery uptake.

2020 - 2019 update of the European AIDS Clinical Society Guidelines for treatment of people living with HIV version 10.0 [Articolo su rivista]
Ryom, L; Cotter, A; De Miguel, R; Béguelin, C; Podlekareva, D; Arribas, J R; Marzolini, C; Mallon, Pgm; Rauch, A; Kirk, O; Molina, J M; Guaraldi, G; Winston, A; Bhagani, S; Cinque, P; Kowalska, J D; Collins, S; Battegay, M
abstract

Background The European AIDS Clinical Society (EACS) Guidelines cover key aspects of HIV management with major updates every two years. Guideline highlights The 2019 Guidelines were extended with a new section focusing on drug-drug interactions and other prescribing issues in people living with HIV (PLWH). The recommendations for treatment-naive PLWH were updated with four preferred regimens favouring unboosted integrase inhibitors. A two-drug regimen with dolutegravir and lamivudine, and a three-drug regimen including doravirine were also added to the recommended initial regimens. Lower thresholds for hypertension were expanded to all PLWH and for cardiovascular disease prevention, the 10-year predicted risk threshold for consideration of antiretroviral therapy (ART) modification was lowered from 20% to 10%. Frailty and obesity were added as new topics. It was specified to use urine albumin to creatinine ratio to screen for glomerular disease and urine protein to creatinine ratio for tubular diseases, and thresholds were streamlined with the Kidney Disease: Improving Global Outcomes (KDIGO) recommendations. Hepatitis C virus (HCV) treatment recommendations were split into preferred and alternative treatment options. The algorithm for management of recently acquired HCV infection was updated and includes recommendations for early chronic infection management. Treatment of resistant tuberculosis (TB) was streamlined with the World Health Organization (WHO) recommendations, and new tables on immune reconstitution inflammatory syndrome, on when to start ART in the presence of opportunistic infections and on TB drug dosing were included. Conclusions The EACS Guidelines underwent major revisions of all sections in 2019. They are available in four different formats including a new interactive web-based version and are translated into Chinese, French, German, Japanese, Portuguese, Russian and Spanish.

2019 - Abacavir, nevirapine, and ritonavir modulate intracellular calcium levels without affecting GHRH-mediated growth hormone secretion in somatotropic cells in vitro [Articolo su rivista]
Brigante, G; Riccetti, L; Lazzaretti, C; Rofrano, L; Sperduti, S; Potì, F; Diazzi, C; Prodam, F; Guaraldi, G; Lania, Ag; Rochira, V; Casarini, L
abstract

Growth Hormone (GH) deficiency is frequent in HIV-infected patients treated with antiretroviral therapy. We treated GH3 cells with antiretrovirals (nevirapine, ritonavir or abacavir sulfate; 100 pM-1 mM range), after transfection with human growth hormone releasing hormone (GHRH) receptor cDNA. Cells viability, intracellular cAMP, phosphorylation of CREB and calcium increase, GH production and secretion were evaluated both in basal condition and after GHRH, using MTT, bioluminescence resonance energy transfer, western blotting and ELISA. Antiretroviral treatment did not affect GHRH 50% effective dose (EC50) calculated for 30-min intracellular cAMP increase (Mann-Whitney's U test; p ≥ 0.05; n = 4) nor 15-min CREB phosphorylation. The kinetics of GHRH-mediated, rapid intracellular calcium increase was perturbed by pre-incubation with drugs, while GHRH failed to induce the ion increase in ritonavir pre-treated cells (ANOVA; p < 0.05; n = 3). Antiretrovirals did not impact 24-h intracellular and extracellular GH levels (ANOVA; p ≥ 0.05; n = 3). We demonstrated the association between antiretrovirals and intracellular calcium increase, without consequences on somatotrope cells viability and GH synthesis. Overall, these results suggest that antiretrovirals may not directly impact on GH axis in HIV-infected patients.

2019 - Accuracy of imaging methods for steatohepatitis diagnosis in non-alcoholic fatty liver disease patients: A systematic review [Articolo su rivista]
Besutti, Giulia; Valenti, Luca; Ligabue, Guido; Bassi, Maria Chiara; Pattacini, Pierpaolo; Guaraldi, Giovanni; Giorgi Rossi, Paolo
abstract

Non-invasive tests to diagnose non-alcoholic steatohepatitis (NASH) are urgently needed. This systematic review aims to evaluate imaging accuracy in diagnosing NASH among non-alcoholic fatty liver disease (NAFLD) patients, using liver biopsy as reference.

2019 - Age of HIV Acquisition Affects the Risk of Multi-Morbidity after 25 Years of Infection Exposure [Articolo su rivista]
Guaraldi, G; Malagoli, A; Milic, J; Pintassilgo, I; Rossi, E; Riva, N; Franconi, I; Santoro, A; Sorin, P; Streinu-Cercel, A; De Rosa, M; Mussini, C
abstract

Introduction: Understanding the intersection of HIV, aging and health is crucial due to the increasing number of people aging with HIV. Objective: The objective of the study was to assess the prevalence of, and risk factors for individual comorbidities and multi-morbidity in people living with HIV with similar duration of HIV infection, notwithstanding a 25-year difference at the time of HIV acquisition. Methods: In a cross-sectional multicentre retrospective study, we compared three match-control age groups. The "Young" were selected from Romania and included HIV-positive patients prenatally infected and assessed at the age of 25-30 years. The "Old" and the "Geriatric" were selected from Italy. These respectively included subjects infected with HIV at the age of 25 years and assessed at the age of 50-55 years, and those infected at the age of 50 years and assessed at the age of 75-80 years. Each group was sex and age matched in a 1: 5 ratio with controls selected from the CINECA ARNO database from Italy. We described non-infectious comorbidities (NICM), including cardiovascular disease, hypertension, dyslipidaemia, diabetes, chronic kidney disease, and multi-morbidity (MM >= 3 NICM). Results: MM prevalence in the "Young" group compared to controls was 6.2% vs 0%, while in the "Geriatric" was "68.2% vs 3.6%. Using "Young" as a reference, in multivariate analyses, predictors for MM were as follows: HIV serostatus (OR=47.75, IQR 14.78-154.25, p<0.01) and "Geriatric" vs "Young" (OR=30.32, IQR 5.89-155.98, p<0.01). Conclusion: These data suggest that age at acquisition of HIV should be considered as a risk factor for NICM and MM.

2019 - Aging with HIV [Articolo su rivista]
Guaraldi, G.; Milic, J.; Mussini, C.
abstract

Purpose of Review: This review points out unmet medical needs and open research questions of older adults living with HIV. Starting from the definition of aging in HIV, it explores the mosaic of this condition at epidemiological, pathophysiological, and clinical level. Antiretroviral management and diverse models of care are critically discussed. Recent Findings: Aging cohorts suggest HIV as a paradigm of chronic inflammation and immune activation with specific aging trajectory patterns in which antiretroviral therapy may play a role. In the absence of randomized clinical trials, observational cohorts show that therapy is driven by duration of HIV infection and burden of non-infectious comorbidities. Summary: This review suggests that geriatric approach should be used to recognize the complexity of aging goes beyond the viro-immunological success and management of progressive accumulation of non-communicable diseases. This requires recognition of frailty and geriatric syndromes to stratify patients’ diversity by using comprehensive geriatric assessment tools.

2019 - Antiviral activity of sirolimus in an HIV-positive kidney transplant recipient [Articolo su rivista]
Alfano, G.; Fontana, F.; Mori, G.; Vicari, Emanuela; Dolci, G.; Franceschini, E.; Guaraldi, G.; Mussini, C.; Cappelli, G.
abstract

Sirolimus (SIR) is a potent immunosuppressive agent with multiple proprieties. We report beneficial antiviral effects of SIR in an HIV-positive kidney transplant recipient who experienced low-level HIV-1 replication. The immunosuppressive agent was well tolerated by the patient, and no side effects were reported during follow-up. Despite immunosuppressive monotherapy, SIR ensured stable graft function.

2019 - Compression of frailty in adults living with HIV [Articolo su rivista]
Guaraldi, G.; Francesco, D. D.; Malagoli, A.; Zona, S.; Franconi, I.; Santoro, A.; Mussini, C.; Mussi, C.; Cesari, M.; Theou, O.; Rockwood, K.
abstract

Background: Contemporary HIV care may reduce frailty in older adults living with HIV (OALWH). Objective of the study was to estimate prevalence of frailty at the age of 50 and 75 years, and build a model to quantify the burden of frailty in the year 2030. Methods: This study included OALWH attending Modena HIV Metabolic Clinic between 2009 and 2015. Patients are referred from more than 120 HIV clinics well distributed across Italy, therefore being country representative. Our model forecasts the new entries on yearly basis up to 2030. Changes in frailty over a one-year period using a 37-variable frailty index (FI) and death rates were modelled using a validated mathematical algorithm with parameters adjusted to best represent the changes observed at the clinic. In this study, we assessed the number of frailest individuals (defined with a FI &gt; 0.4) at the age of 50 and at the age 75 by calendar year. Results: In the period 2015-2030 we model that frailest OALWH at age 50 will decrease from 26 to 7%, and at the age of 75 years will increase from 43 to 52%. This implies a shift of the frailty prevalence at an older age. Conclusion: We have presented projections of how the burden of frailty in older adults, living with HIV will change. We project fewer people aged 50+ with severe frailty, most of whom will be older than now. These results suggest a compression of age-related frailty.

2019 - Daclatasvir-based regimens in HCV cirrhosis: experience from the Italian early access program [Articolo su rivista]
Calvaruso, Vincenza; Mazzarelli, Chiara; Milazzo, Laura; Badia, Lorenzo; Pasulo, Luisa; Guaraldi, Giovanni; Lionetti, Raffaella; Villa, Erica; Borghi, Vanni; Carrai, Paola; Alberti, Alfredo; Biolato, Marco; Piai, Guido; Persico, Marcello; Santantonio, Teresa; Felder, Martina; Angelico, Mario; Montalbano, Marzia; Mancusi, Rossella Letizia; Grieco, Antonio; Angeli, Elena; D'Offizi, Gianpiero; Fagiuoli, Stefano; Belli, Luca; Verucchi, Gabriella; Puoti, Massimo; Craxì, Antonio
abstract

We reported the efficacy and safety data for daclatasvir (DCV)-based all-oral antiviral therapy in patients treated in the Italian compassionate-use program. 275 patients were included (202 male-73.5%, mean age: 57.4 years, 62 HIV-coinfected, 94 with recurrence of hepatitis C post-OLT). Forty-nine patients (17.8%) had Child-Pugh B, Genotype(G) distribution was: G1a:72 patients (26.2%), G1b:137 (49.8%); G3:40 (14.5%) and G4:26 (9.5%). Patients received DCV with sofosbuvir(SOF) (n = 221, 129 with ribavirin(RBV) or with simeprevir (SMV) or asunaprevir (ASU) (n = 54, 19 with RBV) for up to 24 weeks. Logistic regression was used to identify baseline characteristics associated with sustained virological response at week 12 post-treatment (SVR12). Liver function changes between baseline and follow up were assessed in 228 patients. 240 patients achieved SVR12 (87.3%), post transplant and HIV co-infected patients were equally distributed among SVR and no SVR (35% vs 34.3%; p = 0.56 and 24.2% vs 11.4%, p = 0.13, respectively). SVR rate was significantly higher with the combination DCV + SOF compared with DCV + SIM or ASU (93.2% vs 63.0%, p < 0.0001). Bilirubin value (OR: 0.69, CI95%: 0.54-0.87, p = 0.002) and regimen containing SOF (OR: 9.99, CI95%: 4.09-24.40; p < 0.001) were independently related with SVR. Mean albumin and bilirubin values significantly improved between baseline and follow-up week 12. DCV-based antiviral therapy was well tolerated and resulted in a high SVR when combined with SOF either in pre-transplant and in OLT patients and in "difficult to treat" HCV genotypes. Regimens containing DCV in combination with NS3 protease inhibitors obtained suboptimal results.

2019 - Durability of different initial regimens in HIV-infected patients starting antiretroviral therapy with CD4+ counts <200 cells/mm3 and HIV-RNA >5 log10 copies/mL [Articolo su rivista]
Gianotti, N.; Lorenzini, P.; Cozzi-Lepri, A.; De Luca, A.; Madeddu, G.; Sighinolfi, L.; Pinnetti, C.; Santoro, C.; Meraviglia, P.; Mussini, C.; Antinori, A.; D'Arminio Monforte, A.; D'Arminio Monforte, A.; Andreoni, M.; Angarano, G.; Antinori, A.; Castelli, F.; Cauda, R.; Di Perri, G.; Galli, M.; Iardino, R.; Ippolito, G.; Lazzarin, A.; Perno, C. F.; Von Schloesser, F.; Viale, P.; D'Arminio Monforte, A.; Antinori, A.; Castagna, A.; Ceccherini-Silberstein, F.; Cozzi-Lepri, A.; Girardi, E.; Lo Caputo, S.; Mussini, C.; Puoti, M.; Andreoni, M.; Ammassari, A.; Antinori, A.; Balotta, C.; Bandera, A.; Bonfanti, P.; Bonora, S.; Borderi, M.; Calcagno, A.; Calza, L.; Capobianchi, M. R.; Castagna, A.; Ceccherini-Silberstein, F.; Cingolani, A.; Cinque, P.; Cozzi-Lepri, A.; D'Arminio Monforte, A.; De Luca, A.; Di Biagio, A.; Girardi, E.; Gianotti, N.; Gori, A.; Guaraldi, G.; Lapadula, G.; Lichtner, M.; Lo Caputo, S.; Madeddu, G.; Maggiolo, F.; Marchetti, G.; Marcotullio, S.; Monno, L.; Mussini, C.; Nozza, S.; Puoti, M.; Quiros Roldan, E.; Rossotti, R.; Rusconi, S.; Santoro, M. M.; Saracino, A.; Zaccarelli, M.; Cozzi-Lepri, A.; Fanti, I.; Galli, L.; Lorenzini, P.; Rodano, A.; Shanyinde, M.; Tavelli, A.; Carletti, F.; Carrara, S.; Di Caro, A.; Graziano, S.; Petrone, F.; Prota, G.; Quartu, S.; Truffa, S.; Giacometti, A.; Costantini, A.; Valeriani, C.; Angarano, G.; Monno, L.; Santoro, C.; Maggiolo, F.; Suardi, C.; Viale, P.; Donati, V.; Verucchi, G.; Castelli, F.; Quiros, E.; Minardi, C.; Quirino, T.; Abeli, C.; Manconi, P. E.; Piano, P.; Cacopardo, B.; Celesia, B.; Vecchiet, J.; Falasca, K.; Sighinolfi, L.; Segala, D.; Mazzotta, F.; Vichi, F.; Cassola, G.; Viscoli, C.; Alessandrini, A.; Bobbio, N.; Mazzarello, G.; Mastroianni, C.; Belvisi, V.; Bonfanti, P.; Caramma, I.; Chiodera, A.; Castelli, A. P.; Galli, M.; Lazzarin, A.; Rizzardini, G.; Puoti, M.; D'Arminio Monforte, A.; Ridolfo, A. L.; Piolini, R.; Castagna, A.; Salpietro, S.; Carenzi, L.; Moioli, M. C.; Tincati, C.; Marchetti, G.; Mussini, C.; Puzzolante, C.; Gori, A.; Lapadula, G.; Abrescia, N.; Chirianni, A.; Borgia, G.; Di Martino, F.; Maddaloni, L.; Gentile, I.; Orlando, R.; Baldelli, F.; Francisci, D.; Parruti, G.; Ursini, T.; Magnani, G.; Ursitti, M. A.; Cauda, R.; Andreoni, M.; Antinori, A.; Vullo, V.; Cristaudo, A.; Cingolani, A.; Baldin, G.; Cicalini, S.; Gallo, L.; Nicastri, E.; Acinapura, R.; Capozzi, M.; Libertone, R.; Savinelli, S.; Latini, A.; Cecchetto, M.; Viviani, F.; Mura, M. S.; Madeddu, G.; De Luca, A.; Rossetti, B.; Caramello, P.; Di Perri, G.; C Orofino, G.; Bonora, S.; Sciandra, M.; Bassetti, M.; Londero, A.; Pellizzer, G.; Manfrin, V.
abstract

Objectives: Our aim was to investigate the durability of different initial regimens in patients starting ART with CD4+ counts &lt;200 cells/mm(3) and HIV-RNA &gt;5 log(10) copies/mL.Methods: This was a retrospective study of HIV-infected patients prospectively followed in the ICONA cohort. Those who started ART with boosted protease inhibitors (bPIs), NNRTIs or integrase strand transfer inhibitors (InSTIs), with CD4+ &lt;200 cells/mm(3) and HIV-RNA &gt;5 log(10) copies/mL, were included. The primary endpoint was treatment failure (TF), a composite endpoint defined as virological failure (VF, first of two consecutive HIV-RNA &gt;50 copies/mL after 6 months of treatment), discontinuation of class of the anchor drug or death. Independent associations were investigated by Poisson regression analysis in a model including age, gender, mode of HIV transmission, CDC stage, HCV and HBV co-infection, pre-treatment HIV-RNA, CD4+ count and CD4+/CD8+ ratio, ongoing opportunistic disease, fibrosis FIB-4 index, estimated glomerular filtration rate, haemoglobin, platelets, neutrophils, calendar year of ART initiation, anchor drug class (treatment group) and nucleos(t)ide backbone.Results: A total of 1195 patients fulfilled the inclusion criteria: 696 started ART with a bPI, 315 with an InSTI and 184 with an NNRTI. During 2759 person-years of follow up, 642 patients experienced TF. Starting ART with bPIs [adjusted incidence rate ratio (aIRR) (95% CI) 1.62 (1.29-2.03) versus starting with NNRTIs; P &lt; 0.001] and starting ART with InSTIs [aIRR (95% CI) 0.68 (0.48-0.96) versus starting with NNRTIs; P = 0.03] were independently associated with TF.Conclusions: In patients starting ART with &lt;200 CD4+ cells/mm(3) and &gt;5 log10 HIV-RNA copies/mL, the durability of regimens based on InSTIs was longer than that of NNRTI- and bPI-based regimens.

2019 - Effectiveness of dolutegravir-based regimens as either first-line or switch antiretroviral therapy: data from the Icona cohort [Articolo su rivista]
Mondi, A.; Cozzi-Lepri, A.; Tavelli, A.; Rusconi, S.; Vichi, F.; Ceccherini-Silberstein, F.; Calcagno, A.; De Luca, A.; Maggiolo, F.; Marchetti, G.; Antinori, A.; d'Arminio Monforte, A.; Andreoni, M.; Castagna, A.; Castelli, F.; Cauda, R.; Di Perri, G.; Galli, M.; Iardino, R.; Ippolito, G.; Azzarin, A.; Rezza, G.; von Schloesser, F.; Viale, P.; Ceccherini-Silberstein, F.; Cozzi-Lepri, A.; Girardi, E.; Lo Caputo, S.; Mussini, C.; Puoti, M.; Perno, C. F.; Balotta, C.; Bandera, A.; Bonora, S.; Borderi, M.; Capetti, A.; Capobianchi, M. R.; Cicalini, S.; Cingolani, A.; Cinque, P.; Di Biagio, A.; Gianotti, N.; Gori, A.; Guaraldi, G.; Lapadula, G.; Lichtner, M.; Madeddu, G.; Maggiolo, F.; Monno, L.; Nozza, S.; Quiros Roldan, E.; Rossotti, R.; Rusconi, S.; Santoro, M. M.; Aracino, A.; Sarmati, L.; Fanti, I.; Galli, L.; Lorenzini, P.; Rodano', A.; Macchia, M.; Tavelli, A.; Carletti, F.; Carrara, S.; Di Caro, A.; Graziano, S.; Petrone, F.; Prota, G.; Quartu, S.; Truffa, S.; Giacometti, I. A.; Costantini, A.; Barocci, V.; Angarano, G.; Fabrizio, C.; Suardi, C.; I, V.; Verucchi, G.; Castelnuovo, F.; Minardi, C.; Menzaghi, B.; Abeli, C.; Cacopardo, B.; Celesia, B.; Vecchiet, J.; Falasca, K.; Pan, A.; Lorenzotti, S.; Sighinolfi, L.; Segala, D.; Blanc, P.; Cassola, G.; Viscoli, C.; Lessandrini, A.; Bobbio, N.; Mazzarello, G.; Pozzetto, I.; Bonfanti, P.; Molteni, C.; Chiodera, A.; Milini, P.; Nunnari, G.; Pellicano, G.; Rizzardini, G.; Bai, F.; Moioli, M. C.; Piolini, R.; Ridolfo, A. L.; Salpietro, S.; Tincati, C.; Puzzolante, C.; Migliorino, C.; Sangiovanni, V.; Borgia, G.; Esposito, V.; Di Martino, F.; Gentile, I.; Maddaloni, L.; Cattelan, A. M.; Marinello, S.; Cascio, A.; Colomba, C.; Baldelli, F.; Schiaroli, E.; Parruti, G.; Sozio, F.; Magnani, G.; Ursitti, M. A.; Cristaudo, A.; Vullo, V.; Acinapura, R.; Baldin, G.; Capozzi, M.; Rivano Capparucia, M.; Iaiani, G.; Atini, A.; Mastrorosa, I.; Plazzi, M. M.; Savinelli, S.; Vergori, A.; Cecchetto, M.; Viviani, F.; Bagella, P.; Rossetti, B.; Fontana Del Vecchio, R.; Francisci, D.; Di Giuli, C.; Caramello, P.; Orofino, G. C.; Sciandra, M.; Bassetti, M.; Ondero, A.; Pellizzer, G.; Manfrin, V.; Starnini, G.; Alungo, A.
abstract

Introduction: Concerns about dolutegravir (DTG) tolerability in the real-life setting have recently arisen. We aimed to estimate the risk of treatment discontinuation and virological failure of DTG-based regimens from a large cohort of HIV-infected individuals. Methods: We performed a multicentre, observational study including all antiretroviral therapy (ART)-naïve and virologically suppressed treatment-experienced (TE) patients from the Icona (Italian Cohort Naïve Antiretrovirals) cohort who started, for the first time, a DTG-based regimen from January 2015 to December 2017. We estimated the cumulative risk of DTG discontinuation regardless of the reason and for toxicity, and of virological failure using Kaplan–Meier curves. We used Cox regression model to investigate predictors of DTG discontinuation. Results: About 1679 individuals (932 ART-naïve, 747 TE) were included. The one- and two-year probabilities (95% CI) of DTG discontinuation were 6.7% (4.9 to 8.4) and 11.5% (8.7 to 14.3) for ART-naïve and 6.6% (4.6 to 8.6) and 7.6% (5.4 to 9.8) for TE subjects. In both ART-naïve and TE patients, discontinuations of DTG were mainly driven by toxicity with an estimated risk (95% CI) of 4.0% (2.6 to 5.4) and 2.5% (1.3 to 3.6) by one year and 5.6% (3.8 to 7.5) and 4.0% (2.4 to 5.6) by two years respectively. Neuropsychiatric events were the main reason for stopping DTG in both ART-naïve (2.1%) and TE (1.7%) patients. In ART-naïve, a concomitant AIDS diagnosis predicted the risk of discontinuing DTG for any reason (adjusted relative hazard (aRH)&nbsp;=&nbsp;3.38, p&nbsp;=&nbsp;0.001), whereas starting DTG in combination with abacavir (ABC) was associated with a higher risk of discontinuing because of toxicity (aRH&nbsp;=&nbsp;3.30, p&nbsp;=&nbsp;0.009). TE patients starting a DTG-based dual therapy compared to a triple therapy had a lower risk of discontinuation for any reason (adjusted hazard ratio (aHR)&nbsp;=&nbsp;2.50, p&nbsp;=&nbsp;0.037 for ABC-based triple-therapies, aHR&nbsp;=&nbsp;3.56, p&nbsp;=&nbsp;0.012 for tenofovir-based) and for toxicity (aHR&nbsp;=&nbsp;5.26, p&nbsp;=&nbsp;0.030 for ABC-based, aHR&nbsp;=&nbsp;6.60, p&nbsp;=&nbsp;0.024 for tenofovir-based). The one- and two-year probabilities (95% CI) of virological failure were 1.2% (0.3 to 2.0) and 4.6% (2.7 to 6.5) in the ART naïve group and 2.2% (1.0 to 3.3) and 2.9% (1.5 to 4.3) in the TE group. Conclusions: In this large cohort, DTG showed excellent efficacy and optimal tolerability both as first-line and switching ART. The low risk of treatment-limiting toxicities in ART-naïve as well as in treated individuals reassures on the use of DTG in everyday clinical practice.

2019 - Elderly HIV-positive women: A gender-based analysis from the Multicenter Italian “GEPPO” Cohort [Articolo su rivista]
Focà, Emanuele; Magro, Paola; Guaraldi, Giovanni; Riva, Agostino; Cattelan, Anna Maria; De Socio, Giuseppe Vittorio; Costa, Cecilia; Piconi, Stefania; Celesia, Benedetto Maurizio; Nozza, Silvia; Orofino, Giancarlo; Castagna, Antonella; Di Perri, Giovanni; Castelli, Francesco; Calcagno, Andrea
abstract

BACKGROUND: HIV-positive patients are facing age-and disease-related comorbidities. Since gender differences in viro-immunological, clinical and therapeutic features have been described, aim of this analysis was to explore such differences in elderly HIV-positive females compared to males coming from the same cohort. DESIGN: Cross-sectional study. SETTING: Ten Infectious Diseases Center participating to a new multicenter Italian geriatric Cohort aiming at describing health transition over time in HIV-positive individuals. PARTICIPANTS: HIV-positive patients aged ≥65 years old. MEASUREMENTS: We recorded clinical, viro-immunological and therapeutical data. RESULTS: We included 210 women (17%) out of 1237 patients. Compared to males, elderly females were less likely to present a HIV-RNA &lt;50 copies/mL (74.3% vs. 81.8%, OR 0.64, 95%CI 0.44-0.93); they showed higher CD4+/CD8+ ratio (p = 0.016). Combined antiretroviral therapy (cART) strategies were similar between genders (p&gt;0.05), although women were less likely to be treated with protease Inhibitors (PIs) (p = 0.05); specifically, in triple-drug regimens females received less PIs (28% vs 38% p = 0.022) and more integrase inhibitors (30% vs. 20% p = 0.012). Bone disease was more common in females (p&lt;0.001) while males presented more frequently cardiovascular disease (CVD) (p&lt;0.001). In females with bone disease, PIs and boosted regimens (38% vs. 53.7% p = 0.026 and 30.4 vs 44.0% p = 0.048 respectively) were prescribed less frequently. Polypharmacy was common and similar in both genders (20% vs. 22.8%, p = &gt;0.05). A higher use of lipid-lowering drugs (20.5% vs. 14.8%, p = 0.04) was observed in females and yet they were less likely to receive anti-thrombotic agents (18.6% vs. 26.3%, p = 0.019) even when CVD was recorded (57.1% vs. 83.1%, p = 0.018). In multivariate analysis, we found that female gender was independently associated with a higher CD4+/CD8+ ratio but not with virological suppression. CONCLUSIONS: Elderly HIV-positive women display a worse virologic response despite a better immune reconstitution compared to males. The burden of comorbidities as well as the medications received (including cART) may slightly differ according to gender. Our data suggest that more efforts and focused interventions are needed in this population.

2019 - Establishing a hepatitis C continuum of care among HIV/hepatitis C virus-coinfected individuals in EuroSIDA [Articolo su rivista]
Amele, S.; Peters, L.; Sluzhynska, M.; Yakovlev, A.; Scherrer, A.; Domingo, P.; Gerstoft, J.; Viard, J. P.; Gisinger, M.; Flisiak, R.; Bhaghani, S.; Ristola, M.; Leen, C.; Jablonowska, E.; Wandeler, G.; Stellbrink, H.; Falconer, K.; D'Arminio Monforte, A.; Horban, A.; Rockstroh, J. K.; Lundgren, J. D.; Mocroft, A.; Losso, M.; Kundro, M.; Schmied, B.; Zangerle, R.; Karpov, I.; Vassilenko, A.; Mitsura, V. M.; Paduto, D.; Clumeck, N.; De Wit, S.; Delforge, M.; Florence, E.; Vandekerckhove, L.; Hadziosmanovic, V.; Begovac, J.; Machala, L.; Jilich, D.; Sedlacek, D.; Kronborg, G.; Benfield, T.; Katzenstein, T.; Pedersen, C.; Johansen, I. S.; Ostergaard, L.; Wiese, L.; Moller, N. F.; Nielsen, L. N.; Zilmer, K.; Smidt, J.; Aho, I.; Girard, P. -M.; Pradier, C.; Fontas, E.; Duvivier, C.; Behrens, G.; Degen, O.; Stefan, C.; Bogner, J.; Fatkenheuer, G.; Chkhartishvili, N.; Gargalianos, P.; Xylomenos, G.; Armenis, K.; Sambatakou, H.; Szlavik, J.; Gottfredsson, M.; Mulcahy, F.; Yust, I.; Turner, D.; Burke, M.; Shahar, E.; Hassoun, G.; Elinav, H.; Haouzi, M.; Elbirt, D.; Sthoeger, Z. M.; Esposito, R.; Mazeu, I.; Mussini, C.; Mazzotta, F.; Gabbuti, A.; Vullo, V.; Lichtner, M.; Zaccarelli, M.; Antinori, A.; Acinapura, R.; Plazzi, M.; Lazzarin, A.; Castagna, A.; Gianotti, N.; Galli, M.; Ridolfo, A.; Rozentale, B.; Uzdaviniene, V.; Matulionyte, R.; Staub, T.; Hemmer, R.; Reiss, P.; Reikvam, D. H.; Maeland, A.; Bruun, J.; Knysz, B.; Gasiorowski, J.; Inglot, M.; Bakowska, E.; Grzeszczuk, A.; Parczewski, M.; Maciejewska, K.; Aksak-Was, B.; Beniowski, M.; Mularska, E.; Smiatacz, T.; Gensing, M.; Kamerys, J.; Wojcik, K.; Mozer-Lisewska, I.; Caldeira, L.; Mansinho, K.; Maltez, F.; Radoi, R.; Oprea, C.; Panteleev, A.; Panteleev, O.; Trofimora, T.; Khromova, I.; Kuzovatova, E.; Borodulina, E.; Vdoushkina, E.; Jevtovic, D.; Tomazic, J.; Miro, J. M.; Laguno, M.; Martinez, E.; Garcia, F.; Blanco, J. L.; Martinez-Rebollar, M.; Mallolas, J.; Moreno, S.; Rodriguez, J. M.; Clotet, B.; Jou, A.; Paredes, R.; Tural, C.; Puig, J.; Bravo, I.; Gutierrez, M.; Mateo, G.; Sambeat, M. A.; Laporte, J. M.; Sonnerborg, A.; Treutiger, C. J.; Flamholc, L.; Weber, R.; Cavassini, M.; Calmy, A.; Furrer, H.; Battegay, M.; Schmid, P.; Kuznetsova, A.; Kyselyova, G.; Gazzard, B.; Johnson, A. M.; Simons, E.; Edwards, S.; Phillips, A.; Johnson, M. A.; Orkin, C.; Weber, J.; Scullard, G.; Clarke, A.; Rasmussen, L. D.; Svedhem, V.; Kowalska, J. D.; Guaraldi, G.; Kirk, O.; Bojesen, A.; Raben, D.; Kristensen, D.; Laut, K.; Larsen, J. F.; Podlekareva, D.; Nykjaer, B.; Cozzi-Lepri, A.; Pelchen-Matthews, A.
abstract

Objectives: The aim of the study was to establish a methodology for evaluating the hepatitis C continuum of care in HIV/hepatitis C virus (HCV)-coinfected individuals and to characterize the continuum in Europe on 1 January 2015, prior to widespread access to direct-acting antiviral (DAA) therapy. Methods: Stages included in the continuum were as follows: anti-HCV antibody positive, HCV RNA tested, currently HCV RNA positive, ever HCV RNA positive, ever received HCV treatment, completed HCV treatment, follow-up HCV RNA test, and cure. Sustained virological response (SVR) could only be assessed for those with a follow-up HCV RNA test and was defined as a negative HCV RNA result measured &gt; 12 or 24&nbsp;weeks after stopping treatment. Results: Numbers and percentages for the stages of the HCV continuum of care were as follows: anti-HCV positive (n&nbsp;=&nbsp;5173), HCV RNA tested (4207 of 5173; 81.3%), currently HCV RNA positive (3179 of 5173; 61.5%), ever HCV RNA positive (n&nbsp;=&nbsp;3876), initiated HCV treatment (1693 of 3876; 43.7%), completed HCV treatment (1598 of 3876; 41.2%), follow-up HCV RNA test to allow SVR assessment (1195 of 3876; 30.8%), and cure (629 of 3876; 16.2%). The proportion that achieved SVR was 52.6% (629 of 1195). There were significant differences between regions at each stage of the continuum (P&nbsp;&lt;&nbsp;0.0001). Conclusions: In the proposed HCV continuum of care for HIV/HCV-coinfected individuals, we found major gaps at all stages, with almost 20% of anti-HCV-positive individuals having no documented HCV RNA test and a low proportion achieving SVR, in the pre-DAA era.

2019 - European cohorts of older HIV adults: POPPY, AGEhIV, GEPPO, COBRA and FUNCFRAIL [Articolo su rivista]
Milic, J.; Russwurm, M.; Cerezales Calvino, A.; Branas, F.; Sanchez-Conde, M.; Guaraldi, G.
abstract

Aim: The recent and rapid demographic changes affecting people living with HIV (PLWH) produced a subset of older adults demanding a prompt response both in clinical practice and research setting. The scientific community had to properly design studies that include older adults living with HIV (OALWH), aged &gt;&nbsp;50&nbsp;years, or geriatric PLWH, aged &gt;&nbsp;65&nbsp;years to explore the interaction between aging and HIV itself, antiretroviral therapy (ART) and non-infectious co-morbidities (NICM). Choosing between these two types of&nbsp;cohorts may represent a trap, but also a possibility to measure different outcomes and obtain different evidence.&nbsp;The aim of this paper is to describe ongoing aging HIV cohorts that include older&nbsp;or geriatric PLWH&nbsp;and present the key results obtained in those studies. Methods: So far, in Europe, there are ongoing cohorts that comprise OALWH or geriatric PLWH: AGEhIV, POPPY, GEPPO, FUNCFRAIL and COBRA. We will summarize crucial findings from each study published up to now, which will be categorized as results related to HIV and ART, NICM and geriatric syndromes. Results: Existing aging HIV cohorts are pointing out unmet medical needs of OALWH but are still not representative of the entire European HIV aging epidemic. Moreover, there are no studies designed to detect best ART strategies in this population and various outcomes that go beyond the viro-immunological success are still not routinely part of aging cohorts. Conclusion: Results from aging cohorts with outcomes that go beyond the undetectability will pave the way to health care providers to encounter unmet needs of OALWH.

2019 - Evolution of major non-HIV-related comorbidities in HIV-infected patients in the Italian Cohort of Individuals, Naïve for Antiretrovirals (ICONA) Foundation Study cohort in the period 2004-2014 [Articolo su rivista]
d'Arminio Monforte, A; Diaz-Cuervo, H; De Luca, A; Maggiolo, F; Cingolani, A; Bonora, S; Castagna, A; Girardi, E; Antinori, A; Lo Caputo, S; Guaraldi, G; Cozzi-Lepri, A
abstract

The management of HIV disease is complicated by the incidence of a new spectrum of comorbid noncommunicable diseases (NCDs). It is important to document changes in the prevalence of NCDs over time. The aim of the study was to describe the impact of ageing on HIV markers and on the prevalence of NCDs in people living with HIV (PLWHIV) in the Italian Cohort of Individuals, Naïve for Antiretrovirals (ICONA) seen for care in 2004-2014.

2019 - Fitness tracking wearable devices and a dedicated smart phone app (MySAwH App) to predict quality of life in PLWH: a multi-centre prospective study [Abstract in Atti di Convegno]
Guaraldi, G; Orsini, M; Caselgrandi, A; Malagoli, A; D'Imprima, F; Milic, J; Ghinelli, F; Martoglia, R; Mandreoli, F; Ferrari, D; Liu, G; Bloch, M
abstract

2019 - Free Testosterone (FT) is inversely related to frailty in Human Immunodeficiency Virus (HIV)-Infected Men [Abstract in Atti di Convegno]
De Vincentis, S.; Decaroli, M. C.; Diazzi, C.; Morini, F.; Bertani, D.; Fanelli, F.; Mezzullo, M.; Santi, D.; Tartaro, G.; Baraldi, E.; Tagliavini, S.; Pagotto, U.; Guaraldi, G.; Rochira., V.
abstract

2019 - Free testosterone (FT) is inversely related to frailty in human immunodeficiency virus (HIV)-infected men. [Abstract in Atti di Convegno]
De Vincentis, S.; Decaroli, M. C.; Diazzi, C.; Morini, F.; Bertani, D.; Fanelli, F.; Mezzullo, M.; Santi, D.; Tartaro, G.; Baraldi, E.; Tagliavini, S.; Pagotto, U.; Guaraldi, G.; Rochira., V.
abstract

BACKGROUND HIV-infection is associated to several age-related comorbidities, such as a premature decline of serum testosterone (T). There is evidence about the relationship between health status, represented by frailty and comorbidities, and serum T levels in general population, while only one previous retrospective study investigated it in HIV-infected men. AIM To investigate the association between frailty and gonadal status by assessing serum total T (TT) with Liquid Chromatography tandem Mass Spectrometry (LC-MS/MS) in a cohort of HIV-infected men. METHODS Prospective, cross-sectional, observational study on HIV-infected men (age years) with ongoing Highly Active Antiretroviral Therapy (HAART). Serum TT was assessed by the gold standard ID- LC-MS/MS. Sex hormone-binding globulin (SHBG) was measured by chemiluminescent immunoassay. Free T (FT) was calculated by Vermeulen equation. Frailty was calculated through -items multimorbidity frailty index. Saca aa Parameters were not normally distributed and Mann- Whitney U test was used to compare continuous variables. Correlations were performed using linear regression models. RESULTS consecutive HIV-infected men were enrolled (mean age .. years; average duration of HIV-infection .. years). patients (.) had TT below ng/dL and patients (.) had calculated FT below pg/mL. Overall, patients (.) had T deficiency defined by low TT levels and/or low FT. patients (.) showed SHBG above the normal range (. nmol/L). Frailty score (p.), age (p.), duration of HIV-infection and of HAART (p.) significantly differed between eugonadic and hypogonadic patients, while no difference was found for BMI (p.). FT inversely correlated with frailty score (p., R.), while TT did not (p.). At stepwise multivariate regression analysis, FT showed an inverse relation with age (p.,R.), years of infection (-.,p.,R.) and years of HAART (-.,p.,R.), but not with frailty score and BMI of patients. CONCLUSIONS To the best of our knowledge, this is the first properly-designed prospective study aiming to investigate the relationship between general health status and gonadal function in a cohort of HIV-infected men. FT is inversely related to frailty score, suggesting an impairment of gonadal function in those patients affected by more multimorbidities in this setting as well as in general population. At the same time, the age of patient and the duration of HIV-infection seem to be more potent predictive factors for serum FT levels than frailty score. In clinical practice it is important to check for testosterone in these patients due to frequent alterations of SHBG.

2019 - Gonadal Function in Human Immunodeficiency Virus (HIV)-Infected Men Assessed by Isotopic Dilution-Liquid Chromatography-Tandem Mass Spectrometry (ID-LC-MS/MS) and Chemiluminescent Immunoassay. [Abstract in Atti di Convegno]
De Vincentis, S.; Decaroli, M. C.; Diazzi, C.; Morini, F.; Bertani, D.; Fanelli, F.; Mezzullo, M.; Santi, D.; Baraldi, E.; Tagliavini, S.; Pagotto, U.; Guaraldi, G.; Rochira., V.
abstract

2019 - Gonadal Function in Human Immunodeficiency Virus (HIV)-Infected Men: comparison between Isotopic Dilution-Liquid Chromatography- Tandem Mass Spectrometry (ID-LC-MS/MS) and Chemiluminescent Immunoassay (CI). [Abstract in Atti di Convegno]
De Vincentis, S.; Decaroli, M. C.; Fanelli, F.; Mezzullo, M.; Diazzi, C.; Morini, F.; Bertani, D.; Santi, D.; Baraldi, E.; Tagliavini, S.; Roli, L.; Trenti, T.; Pagotto, U.; Guaraldi, G.; Rochira., V.
abstract

2019 - Gonadal function in human immunodeficiency virus (HIV)-infected men: comparison between isotopic dilution-liquid chromatography-tandem mass spectrometry (ID-LC-MS/MS) and chemiluminescent immunoassay (CI) [Abstract in Atti di Convegno]
Decaroli, M. C.; De Vincentis, S.; Fanelli, F.; Mezzullo, M.; Diazzi, C.; Morini, F.; Bertani, D.; Santi, D.; Baraldi, E.; Tagliavini, S.; Roli, L.; Trenti, T.; Pagotto, U.; Guaraldi, G.; Rochira, V.
abstract

2019 - HIV and aging: time to bridge the gap between clinical research and clinical care [Articolo su rivista]
Brañas, Fátima; Guaraldi, Giovanni; Sánchez-Conde, Matilde
abstract

In the short time frame of 30 years, HIV research has been able to modify AIDS from a rapidly progressive disease leading inevitably to death to a chronic condition. Even more, the health status of people living with HIV (PLWH) has significantly improved reducing the burden of symptoms and improving quality of life (QoL). After introduction of the UNAIDS agenda on the “90–90–90 targets”, it remains unclear what should be the next target in HIV care and research. The objective of this paper is to critically discuss potential new outcomes to be used as a measure of success in PLWH both in clinical and research settings. Methods To better portray potential outcomes, we will critically discuss epidemiological and clinical outcomes, patientreported outcomes (PRO), and public health outcomes reported in literature. These outcomes intersect with one another which may suggest contemporary use of different outcomes depending on goals we want to achieve. New outcomes should go beyond undetectability, be patient-centred, and similar to those in geriatric medicine and the general population. Conclusions HIV care can take advantage of experience from geriatric medicine and teach-back by describing aging trajectories in PLWH that may be accentuated in comparison to general population. However, we still need to improve tools to measure quality of life, PROs, and healthy aging. Healthy aging assessment will allow us to recognize unmet needs in PLWH and represents an integrated model between community, the person, and healthcare providers, wherein all stakeholders are linked, increasing possibilities for effective intervention.

2019 - Immediate vs. Deferred Switching from a Boosted Protease Inhibitor (PI/r) Based Regimen to a Dolutegravir (DTG) Based Regimen in Virologically Suppressed Patients with High Cardiovascular Risk or Age ≥50 years: Final 96 Weeks Results of NEAT 022 study [Articolo su rivista]
Gatell, José M; Assoumou, Lambert; Moyle, Graeme; Waters, Laura; Johnson, Margaret; Domingo, Pere; Fox, Julie; Martinez, Esteban; Stellbrink, Hans-Jürgen; Guaraldi, Giovanni; Masia, Mar; Gompels, Mark; De Wit, Stephane; Florence, Eric; Esser, Stefan; Raffi, François; Stephan, Christoph; Rockstroh, Juergen; Giacomelli, Andrea; Vera, Jaime; Bernardino, José Ignacio; Winston, Alan; Saumoy, Maria; Gras, Julien; Katlama, Christine; Pozniak, Anton L
abstract

Both immediate or deferred switching from a PI/r to DTG may improve lipid profile.

2019 - Impact of diabetes on the risk of serious liver events and liver-related deaths in people living with HIV and hepatitis C co-infection: data from the ICONA Foundation Cohort Study [Articolo su rivista]
Leone, S.; Lorenzini, P.; Cozzi-Lepri, A.; Orofino, G.; Bernacchia, D.; Castagna, A.; Menozzi, M.; Guaraldi, G.; Madeddu, G.; Di Biagio, A.; Puoti, M.; Gori, A.; d'Arminio Monforte, A.
abstract

To investigate the association between diabetes and HCV infection in persons living with HIV and to determine the impact of diabetes on the occurrence of serious liver events (SLEs) and liver-related deaths (LRDs) among HIV/HCV-co-infected patients. Patients were included if they had at least one follow-up visit. In a cross-sectional analysis among all HIV patients, we have investigated the association between diabetes and HCV infection. A further longitudinal analysis was performed in the population of HIV/HCV-co-infected free from SLE with FIB-4 index &lt; 3.25 at baseline, using the following endpoints: (A) first event between SLE and LRD; (B) liver fibrosis progression defined as the first of two consecutive FIB-4 &gt; 3.25; (C) first event between SLE, LRD, and liver fibrosis progression. Data from 15,571 HIV patients were analyzed: 2944 (18.9%) were HCV-Ab positive, and 739 (4.7%) presented a diagnosis of diabetes at their last follow-up. Among HIV/HCV-co-infected population, 107 patients had a diagnosis of diabetes. Viremic HCV-co-infected patients had 3-fold risk of diabetes onset than HCV-uninfected patients. On HIV/HCV-co-infected population, 85 SLEs/LRDs occurred over 20,410 person-years of follow-up (PYFU), for an incidence rate of 4.2/1000 PYFU (95%CI 3.4–5.2). Diabetic patients had 3-fold risk of pooled SLE and LRD than patients without diabetes. Furthermore, viremic HCV infection was independently associated with a higher risk of SLE/LRD (aIRR 3.35 [95%CI 1.14–9.83]). In HIV-infected patients, viremic HCV co-infection is a strong predictor of diabetes. Among HIV/HCV-co-infected population, diabetic patients showed an increased risk of SLE/LRD compared with those without diabetes.

2019 - Impact of prolonged maraviroc treatment on non-AIDS-related comorbidities in HIV-positive patients: a retrospective cohort study [Articolo su rivista]
Piconi, Stefania; Foschi, Antonella; Malagoli, Andrea; Carli, Federica; Zona, Stefano; Milic, Jovana; Ricci, Elena Delfina; Rizzardini, Giuliano; Guaraldi, Giovanni
abstract

This retrospective study evaluates the effect of maraviroc, the first CCR5 receptor antagonist, on non-AIDS-related comorbidity incidence and its impact on inflammatory and lipid parameters.

2019 - Is physician assessment of alcohol consumption useful in predicting risk of severe liver disease among people with HIV and HIV/HCV co-infection? [Articolo su rivista]
Shanyinde, M.; Girardi, E.; Puoti, M.; De Luca, A.; Sighinolfi, L.; Caterina, U. F.; Caramello, P.; Lampe, F. C.; D'Arminio Monforte, A.; Cozzi-Lepri, A.; Andreoni, M.; Angarano, G.; Antinori, A.; Castelli, F.; Cauda, R.; Di Perri, G.; Galli, M.; Iardino, R.; Ippolito, G.; Lazzarin, A.; Perno, C. F.; Von Schloesser, F.; Viale, P.; Castagna, A.; Ceccherini-Silberstein, F.; Caputo, S. L.; Mussini, C.; Ammassari, A.; Balotta, C.; Bandera, A.; Bonfanti, P.; Bonora, S.; Borderi, M.; Calcagno, A.; Calza, L.; Capobianchi, M. R.; Cingolani, A.; Cinque, P.; Di Biagio, A.; Gianotti, N.; Gori, A.; Guaraldi, G.; Lapadula, G.; Lichtner, M.; Madeddu, G.; Maggiolo, F.; Marchetti, G.; Marcotullio, S.; Monno, L.; Nozza, S.; Roldan, E. Q.; Rossotti, R.; Rusconi, S.; Santoro, M. M.; Saracino, A.; Zaccarelli, M.; Fanti, I.; Galli, L.; Lorenzini, P.; Rodano, A.; Tavelli, A.; Carletti, F.; Carrara, S.; Di Caro, A.; Graziano, S.; Petrone, F.; Prota, G.; Quartu, S.; Truffa, S.; Giacometti, A.; Costantini, A.; Valeriani, C.; Santoro, C.; Suardi, C.; Donati, V.; Verucchi, G.; Minardi, C.; Quirino, T.; Abeli, C.; Manconi, P. E.; Piano, P.; Cacopardo, B.; Celesia, B.; Vecchiet, J.; Falasca, K.; Segala, D.; Mazzotta, F.; Vichi, F.; Cassola, G.; Viscoli, C.; Alessandrini, A.; Bobbio, N.; Mazzarello, G.; Mastroianni, C.; Belvisi, V.; Caramma, I.; Chiodera, A.; Milini, P.; Rizzardini, G.; Ridolfo, A. L.; Piolini, R.; Salpietro, S.; Carenzi, L.; Moioli, M. C.; Tincati, C.; Puzzolante, C.; Abrescia, N.; Chirianni, A.; Borgia, G.; Orlando, R.; Di Martino, F.; Maddaloni, L.; Gentile, I.; Bonadies, G.; Cascio, A.; Colomba, C.; Baldelli, F.; Schiaroli, E.; Parruti, G.; Ursini, T.; Magnani, G.; Ursitti, M. A.; Vullo, V.; Cristaudo, A.; Baldin, G.; Cicalini, S.; Gallo, L.; Nicastri, E.; Acinapura, R.; Capozzi, M.; Libertone, R.; Savinelli, S.; Latini, A.; Iaiani, G.; Sulekova, L. F.; Cecchetto, M.; Viviani, F.; Mura, M. S.; Rossetti, B.; Francisci, D.; Di Giuli, C.; Orofino, G. C.; Sciandra, M.; Bassetti, M.; Londero, A.; Pellizzer, G.; Manfrin, V.
abstract

Background: Alcohol consumption is a known risk factor for liver disease in HIV-infected populations. Therefore, knowledge of alcohol consumption behaviour and risk of disease progression associated with hazardous drinking are important in the overall management of HIV disease. We aimed at assessing the usefulness of routine data collected on alcohol consumption in predicting risk of severe liver disease (SLD) among people living with HIV (PLWHIV) with or without hepatitis C infection seen for routine clinical care in Italy. Methods: We included PLWHIV from two observational cohorts in Italy (ICONA and HepaICONA). Alcohol consumption was assessed by physician interview and categorized according to the National Institute for Food and Nutrition Italian guidelines into four categories: abstainer; moderate; hazardous and unknown. SLD was defined as presence of FIB4 &gt; 3.25 or a clinical diagnosis of liver disease or liver-related death. Cox regression analysis was used to evaluate the association between level of alcohol consumption at baseline and risk of SLD. Results: Among 9542 included PLWHIV the distribution of alcohol consumption categories was: abstainers 3422 (36%), moderate drinkers 2279 (23%), hazardous drinkers 637 (7%) and unknown 3204 (34%). Compared to moderate drinkers, hazardous drinking was associated with higher risk of SLD (adjusted hazard ratio, aHR = 1.45; 95% CI: 1.03-2.03). After additionally controlling for mode of HIV transmission, HCV infection and smoking, the association was attenuated (aHR = 1.32; 95% CI: 0.94-1.85). There was no evidence that the association was stronger when restricting to the HIV/HCV co-infected population. Conclusions: Using a brief physician interview, we found evidence for an association between hazardous alcohol consumption and subsequent risk of SLD among PLWHIV, but this was not independent of HIV mode of transmission, HCV-infection and smoking. More efforts should be made to improve quality and validity of data on alcohol consumption in cohorts of HIV/HCV-infected individuals.

2019 - Kidney Disease in HIV Infection [Articolo su rivista]
Alfano, Gaetano; Cappelli, Gianni; Fontana, Francesco; Di Lullo, Luca; Di Iorio, Biagio; Bellasi, Antonio; Guaraldi, Giovanni
abstract

Antiretroviral therapy (ART) has significantly improved life expectancy of infected subjects, generating a new epidemiological setting of people aging withHuman Immunodeficiency Virus (HIV). People living with HIV (PLWH), having longer life expectancy, now face several age-related conditions as well as side effects of long-term exposure of ART. Chronic kidney disease (CKD) is a common comorbidity in this population. CKD is a relentlessly progressive disease that may evolve toward end-stage renal disease (ESRD) and significantly affect quality of life and risk of death. Herein, we review current understanding of renal involvement in PLWH, mechanisms and risk factors for CKD as well as strategies for early recognition of renal dysfunction and best care of CKD.

2019 - La sarcopenia nell’anziano con HIV [Articolo su rivista]
Guaraldi, Giovanni; Milić, Jovana; Guardigni, Viola
abstract

La sarcopenia è una sindrome caratterizzata dalla perdita progressiva e generalizzata di massa scheletrica e forza muscolare associata ad un aumentato rischio di disabilità fisica, bassa qualità di vita, comorbosità e morte. Nella popolazione generale, la perdita di massa muscolare è strettamente dipendente dall’età e dalla quantità di tessuto muscolare raggiunto con l’accrescimento. In condizioni fisiologiche la massa muscolare diminuisce di circa l’1-2% all’anno dopo i 50 anni. Le donne subiscono una perdita accelerata di tessuto muscolare in età più precoce rispetto agli uomini, e questo fenomeno si accelera a partire dalla menopausa; tuttavia, gli uomini perdono più massa muscolare nel corso della loro vita rispetto alle donne.

2019 - Lean mass declines consistently over 10 years in people living with HIV on antiretroviral therapy, with patterns differing by sex [Articolo su rivista]
Debroy, Paula; Lake, Jordan E; Sim, Myung; Erlandson, Kristine M; Falutz, Julian; Prado, Carla M; Brown, Todd T; Guaraldi, Giovanni
abstract

The long-term trajectory of and factors affecting lean mass in people living with HIV (PLWH) are incompletely described.

2019 - Management of human immunodeficiency virus in older people [Articolo su rivista]
Eu, Beng; Salleh, Ethan; Sakko, Andrew; Guaraldi, Giovanni
abstract

The proportion of older (aged ≥50 years) people living with human immunodeficiency virus (PLHIV) within the HIV-positive population is increasing. Many comorbidities associated with ageing are observed more frequently and/or occur at an earlier age among PLHIV, compared with people who are uninfected.

2019 - Migration and health: A retrospective study about the prevalence of HBV, HIV, HCV, tuberculosis and syphilis infections amongst newly arrived migrants screened at the Infectious Diseases Unit of Modena, Italy [Articolo su rivista]
Cuomo, Gianluca; Franconi, Iacopo; Riva, Nicoletta; Bianchi, Alessandro; Digaetano, Margherita; Santoro, Antonella; Codeluppi, Mauro; Bedini, Andrea; Guaraldi, Giovanni; Mussini, Cristina
abstract

Introduction Aim of the study is to evaluate the prevalence of HBV, HIV, HCV, tuberculosis and syphilis infection among immigrants assigned to the immigrant centre of the province of Modena. Methods At the time of arrival all immigrant were tested for: HBsAg, HBsAb, HBcAb, Ag p24/HIVAb, HCVAb, RPR, TPPA, Mantoux test (&gt;10 mm diameter of induration was considered to be positive), Chest X-rays. In case of positive samples, second level tests were performed (HbeAg, HBeAb, HDVAb, and baseline management and treatment of the infection detected). Results A total of 304 immigrant people were enrolled in the study. HBsAg positivity was 12.2%, HCVAb 3.3%, HIVAb 1.6%, TPPA + RPR positivity in the 0.7%; 10.2% had a positive Mantoux test; 5.6% had Chest X-rays positive for signs of infection and 6 patients had an active tuberculosis. 83.8% HBsAg were HBeAb positive/HBeAg negative. HDVAb resulted positive in 1 patient (2.7%). Previous HBV infection was detected in 28.6% of cases, isolated HBcAb in 2.3%; 5.6% of patients resulted to be positive to HbsAb alone (probable vaccinated). Conclusion Our study confirms the high prevalence of HBsAg positivity and latent tuberculosis among immigrants, underlying the importance of screening for infections in this special population.

2019 - Molecular Imaging of Vascular Calcification with 18 F-Sodium-Fluoride in Patients Infected with Human Immunodeficiency Virus [Articolo su rivista]
Raggi, Paolo; Prandini, Napoleone; Ligabue, Guido; Braglia, Giovanni; Esposito, Francesco; Milic, Jovana; Malagoli, Andrea; Scaglioni, Riccardo; Besutti, Giulia; Beghetto, Barbara; Nardini, Giulia; Roncaglia, Enrica; Mussini, Cristina; Guaraldi, Giovanni
abstract

18F-Sodium Fluoride (NaF) accumulates in areas of active hydroxyapatite deposition and potentially unstable atherosclerotic plaques. We assessed the presence of atherosclerotic plaques in 50 adult patients with HIV (HIV+) who had undergone two cardiac computed tomography scans to measure coronary artery calcium (CAC) progression. CAC and its progression are predictive of an unfavorable prognosis. Tracer uptake was quantified in six arterial territories: aortic arch, innominate carotid artery, right and left internal carotid arteries, left coronary (anterior descending and circumflex) and right coronary artery. Thirty-one patients showed CAC progression and 19 did not. At least one territory with high NaF uptake was observed in 150 (50%) of 300 arterial territories. High NaF uptake was detected more often in non-calcified than calcified areas (68% vs. 32%), and in patients without than in those with prior CAC progression (68% vs. 32%). There was no correlation between clinical and demographic variables and NaF uptake. In clinically stable HIV+ patients, half of the arterial territories showed a high NaF uptake, often in the absence of macroscopic calcification. NaF uptake at one time point did not correlate with prior progression of CAC. Prospective studies will demonstrate the prognostic significance of high NaF uptake in HIV+ patients.

2019 - "Moving Fourth": A Vision Toward Achieving Healthy Living with HIV Beyond Viral Suppression [Articolo su rivista]
Guaraldi, Giovanni; Arends, Joop; Buhk, Thomas; Cascio, Mario; Curran, Adrian; Teofilo, Eugenio; Berk, Guido Van Den; Verger, Christian
abstract

Since HIV has evolved from being a fatal illness to a chronic condition, this brings new challenges relating to long-term health, as increasing numbers of people living with HIV (PLHIV) navigate their lives beyond viral suppression. This review presents the challenges facing patients and health-care providers managing HIV in Europe today. We highlight the challenges that the evolving landscape in HIV brings, including managing an aging and more diverse population of PLHIV; this requires a shift from managing disease to managing health and may best be achieved by multidisciplinary teams in the long term. We introduce the concept of "health goals for me:" an individualized approach to the management of HIV, and use this as the basis for a proposed framework for assessing health-related quality of life for PLHIV. Our framework comprises a continuous cycle of "ask and measure," "feedback and discussion," and "intervention," based on collaboration between the health-care professional and patient. For improved long-term management of PLHIV, we consider that this framework should become an intrinsic part of HIV care in the future and that the "health goals for me" concept be used as a tool to facilitate healthy living for PLHIV beyond viral suppression.

2019 - Older HIV-infected adults: complex patients— geriatric syndromes (II) [Articolo su rivista]
Bertagnoli, L.; Iannuzzi, P.; Ciccone, S.; Canevelli, M.; Marzetti, E.; Guaraldi, G.; Cesari, M.
abstract

With the widespread adoption of highly active antiretroviral therapy (HAART), HIV infection starts to be considered one of the many chronic illnesses of advanced age. A growing proportion of the affected patients is presently older than 50. It has been suggested that HIV infection may today represent a model of accelerated and accentuated ageing. The need for a closer collaboration between geriatricians and HIV physicians is being growingly recognised to better address the priori- ties and needs of HIV patients. The final aim behind the generation of such synergies resides in the design of personalised plans of interventions. These plans should stem from the results of a comprehensive assessment of the individual spanning clinical, environmental, and psychosocial domains. Through the early identification of stressors and risk factors potentially disrupting the homeostatic balance of frail patients (including those living with HIV), it might be possible to protect the “biologically old” (but not necessarily “chronologically old”) HIV-infected people from developing detrimental geriatric syndromes. In this article, specific features making the ageing HIV population of special interest for geriatric medicine, and the importance of a multidisciplinary model of care are described. The final objective is to stress how the only way for adequately tackling the multifaceted frailty condition of people with HIV is to implement novel models of care based on the comprehensive geriatric assessment.

2019 - Pneumocystosis as a Complication of H1N1 Influenza A Infection in an HIV-Positive Patient on Effective cART [Articolo su rivista]
Franconi, Iacopo; Monari, Caterina; Tutone, Marco; Ciusa, Giacomo; Corradi, Luca; Franceschini, Erica; Meschiari, Marianna; Puzzolante, Cinzia; Gennari, William; Pecorari, Monica; Guaraldi, Giovanni; Mussini, Cristina
abstract

H1N1 influenza A virus can affect the immune system, causing lymphopenia. This might be of great concern for HIV individuals undergoing effective antireroviral therapy (cART). We report the first confirmed case of H1N1-induced AIDS and Pneumocystis jiroveci pneumonia in an HIV-positive woman on effective cART since 2006.

2019 - Prevalence of thyroid disfunctions in a large cohort of Human Immunodeficiency Virus (HIV)-Infected Patients [Abstract in Atti di Convegno]
Tartaro, G.; De Vincentis, S.; Brigante, G.; Diazzi, C.; Malagoli, A.; Guaraldi, G.; Rochira, V.
abstract

2019 - Progressive increases in fat mass occur in adults living with HIV on antiretroviral therapy, but patterns differ by sex and anatomic depot [Articolo su rivista]
Debroy, Paula; Sim, Myung; Erlandson, Kristine M; Falutz, Julian; Prado, Carla M; Brown, Todd T; Guaraldi, Giovanni; Lake, Jordan E
abstract

Although weight gain on ART is common, the long-term trajectory of and factors affecting increases in fat mass in people living with HIV are not well described.

2019 - Relationship between Grip Strength and Nonalcoholic Fatty Liver Disease in Men Living with HIV Referred to a Metabolic Clinic [Articolo su rivista]
Debroy, P.; Lake, J. E.; Malagoli, A.; Guaraldi, G.
abstract

This study aimed to assess the relationship between grip strength (GS) and nonalcoholic fatty liver (NAFLD) in treated HIV-infected men. We included 169 HIV-infected men. GS was assessed using a hand-grip dynamometer. NALFD was defined by liver-spleen attenuation ratio &lt;1.1 on computed tomography. Mean (SD) age was 57 (6) years and BMI 24.5 (2.9) kg/m2. NAFLD was diagnosed in 33% of men; sarcopenia was present in 28%. Mean (SD) hand grip strength in the dominant hand was 37.5 (7.6) kg. In multivariate logistic regression, intermediate and low GS were associated with higher risk of NAFLD (OR 3.05; CI 1.27-7.61, p=0.01; OR 2.47; CI 1.01-6.19, p=0.05, respectively). GS has an inverse association with NAFLD prevalence in HIV-infected men. Specific mechanisms through which muscle weakness and NAFLD are related require further exploration but are not accounted for merely by the burden of comorbid illness, HIV disease stage, or ART exposure.

2019 - Reliability of calcium-phosphorus (Ca/P) ratio as a new, accurate and inexpensive tool in the diagnosis of some Ca-P disorders. [Articolo su rivista]
Madeo, B.; De Vincentis, S.; Kara, E.; Vescini, F.; Trenti, T.; Guaraldi, G.; Rochira, Vincenzo
abstract

PURPOSE: The serum calcium/phosphorus (Ca/P) ratio is an accurate tool to differentiate patients with primary hyperparathyroidism (PHPT) from healthy subjects. However, other disorders of the Ca-P metabolism might impair the Ca/P ratio, such as hypophosphatemia (HypoP) not PHPT related. The aim of this study is to examine the diagnostic value of Ca/P ratio in the diagnosis of PHPT and HypoP not PHPT related. METHODS: Single-center, retrospective, case-control study, including 150 patients with PHPT and 306 patients with HypoP, compared with 150 controls. HypoP patients were enrolled among HIV-infected patients by selecting those with Fanconi-like syndrome due to antiretroviral treatment. Parameters which were measured were serum Ca, P, parathyroid hormone (PTH), 25-OH vitamin D, albumin and creatinine). RESULTS: The Ca/P ratio was significantly higher in PHPT and HypoP patients, compared to controls (p &lt; 0.0001). At receiver operator characteristic (ROC) curve analysis, the cut-off of 3.56 (2.75 SI) for Ca/P ratio was able to identify patients with PHPT and HypoP (sensitivity 95%; specificity 93%). Among patients with Ca/P ratio above 3.56, the thresholds of 10.3 mg/dL (2.6 mmol/L) for serum Ca (sensitivity 93%; specificity 98%) and 80.5 pg/mL for PTH (sensitivity 91%; specificity 91%) were defined for the specific diagnosis of PHPT. CONCLUSIONS: The Ca/P ratio above 3.56 (2.75 SI) is a highly accurate tool to identify PHPT and HypoP not PHPT-related patients. Thanks to its simplicity, this index can be proposed as a screening and first-line examination in the diagnostic work-up when a disorder of Ca-P metabolism is suspected or should be ruled out.

2019 - Rhodococcus equi Pneumonia in Kidney Transplant Recipient Affected by Acute Intermittent Porphyria: A Case Report [Articolo su rivista]
Alfano, G.; Ventura, P.; Fontana, F.; Marcacci, M.; Ligabue, G.; Scarlini, S.; Franceschini, E.; Codeluppi, M.; Guaraldi, G.; Mussini, C.; Cappelli, G.
abstract

Rhodococcus equi is a gram-positive coccobacillus responsible for severe infections in patients with weakened immune systems. R equi generally causes pnumonia that may evolve into fatal systemic infection if left untreated. Here, we present a case of a 67-year-old woman affected by acute intermittent porphyria (AIP) who developed R equi pneumonia 7 months after kidney transplant. Although clinical features at presentation were nonspecific, lung computed tomography showed right perihilar consolidation with a mass-like appearance causing bronchial obstruction. Appropriate antibiotic including intravenous meropenem and oral azithromycin that was then switched to oral levofloxacin and oral azithromycin along with reduction of immunosuppressive therapy resolved pneumonia without provoking an acute attack of porphyria. AIP limited the choice of antibiotics for the treatment of R equi infection because some potentially porphyrinogenic antibacterial agents were avoided. Based on this experience, azithromycin and meropenem can be safely administered for the treatment of R Equi infection in patients with AIP.

2019 - Serum Sodium Is Inversely Related to Frailty and Bone Mineral Density (BMD) in Human Immunodeficiency Virus (HIV)-Infected Patients [Abstract in Atti di Convegno]
De Vincentis, S.; Decaroli, M. C.; Diazzi, C.; Santi, D.; Carli, F.; Zona, S.; Guaraldi, G.; Rochira, V.
abstract

2019 - Significant chronic airway abnormalities in never-smoking HIV-infected patients [Articolo su rivista]
Besutti, G.; Santoro, A.; Scaglioni, R.; Neri, S.; Zona, S.; Malagoli, A.; Orlando, G.; Beghe, B.; Ligabue, G.; Torricelli, P.; Manfredini, M.; Pellacani, G.; Fabbri, L. M.; Guaraldi, G.
abstract

Objectives The aim of the study was to describe chronic lung disease in HIV-infected never-smokers by looking at clinical, structural and functional abnormalities. Methods This comparative cross-sectional study included 159 HIV-infected never-smoking patients [mean (+/- standard deviation) age 54.6 +/- 9.1 years; 13.2% female; 98.1% with undetectable viral load] and 75 nonmatched never-smoking controls [mean (+/- standard deviation) age 52.6 +/- 6.9 years; 46.7% female]. We examined calcium scoring computer tomography (CT) scans or chest CT scans, all with a lung-dedicated algorithm reconstruction, to assess emphysema and airway disease (respiratory bronchiolitis and/or bronchial wall thickening), tested pulmonary function using spirometry, lung volumes and the diffusion lung capacity of carbon monoxide (DLCO), and assessed respiratory symptoms using the Chronic Obstructive Pulmonary Disease (COPD) Assessment Test (CAT). Results Twenty-five (17.2%) of the HIV-infected patients versus two (2.7%) of the controls had a CAT score &gt; 10. Only 5% of the HIV-infected patients showed FEV1% &lt; 80%, and 25% had DLCO CT scans, they had increased prevalences, compared with the controls, of airway disease (37% versus 7.9%, respectively) and emphysema (18% versus 4%, respectively), with more severe and more frequent centrilobular disease. After correction for age, sex and clinical factors, HIV infection was significantly associated with CAT &gt; 10 [odds ratio (OR) 7.7], emphysema (OR 4), airway disease (OR 4.5) and DLCO &lt; 75% of predicted (OR 4). Conclusions Although comparisons were limited by the different enrolment methods used for HIV-infected patients and controls, the results suggest that never-smoking HIV-infected patients may present with chronic lung damage characterized by CT evidence of airway disease. A minority of them showed respiratory symptoms, without significant functional abnormalities.

2019 - The dynamic association between Frailty, CD4 and CD4/CD8 ratio in people aging with HIV [Articolo su rivista]
Guaraldi, Giovanni; Zona, Stefano; Silva, Ana Rita; Menozzi, Marianna; Dolci, Giovanni; Milic, Jovana; Carli, Federica; Mussini, Cristina
abstract

To investigate the association between current CD4+ T-cell count and CD4/CD8+ ratio with severity of frailty among people aging with HIV.

2019 - The Interplay Between Age and Frailty in People Living With HIV: Results From an 11-Year Follow-up Observational Study [Articolo su rivista]
Guaraldi, Giovanni; De Francesco, Davide; Milic, Jovana; Franconi, Iacopo; Mussini, Cristina; Falutz, Julian; Cesari, Matteo
abstract

Between 2006 and 2017, frailty prevalence decreased in HIV-positive individuals aged 50 years but presented a 3-fold increase among those 75 years of age. This dynamic relationship, defined as the frailty compression ratio, represents the net result of gero-inducing and gero-protective competing forces, described in the cohort.

2019 - The interplay between frailty and intrinsic capacity in aging and HIV infection [Articolo su rivista]
Guaraldi, Giovanni; Milic, Jovana
abstract

In the context of an emerging aging epidemic affecting people living with HIV (PLWH), we critically discuss existing data regarding two different conceptual models of aging - frailty and intrinsic capacity respectively, both in a clinical and public health perspective. These constructs have not yet been integrated in the general population. Nevertheless, the holistic HIV care, that goes beyond the viro-immunological success, may offer an ideal setting to test a possible integration of these models in older adults living with HIV. We suggest a new framework to assess health in PLWH, shifting from an infectious diseases (ID)/internal medicine approach, which includes quality of life in the definition of healthy living with HIV, to an ID/geriatric medicine approach, focused on the maintenance of functional ability in frail and geriatric PLWH.

2019 - The Management of Geriatric and Frail HIV Patients. A 2017 Update from the Italian Guidelines for the Use of Antiretroviral Agents and the Diagnostic Clinical Management of HIV-1 Infected Persons [Articolo su rivista]
Guaraldi, G; Marcotullio, S; Maserati, R; Gargiulo, M; Milic, J; Franconi, I; Chirianni, A; Andreoni, M; Galli, M; Lazzarin, A; D'Arminio Monforte, A; Di Perri, G; Perno, C-F; Puoti, M; Vella, S; Di Biagio, A; Maia, L; Mussi, C; Cesari, M; Antinori, A
abstract

This article deals with the attempt to join HIV and geriatric care management in the 2017 edition of the Italian guidelines for the use of antiretrovirals and the diagnostic-clinical management of HIV-1 infected persons.

2019 - Thymus Imaging Detection and Size Is Inversely Associated With Metabolic Syndrome and Frailty in People With HIV [Articolo su rivista]
Guaraldi, Giovanni; Franconi, Iacopo; Milic, Jovana; Besutti, Giulia; Pintassilgo, Ines; Scaglioni, Riccardo; Ligabue, Guido; Riva, Nicoletta; Raimondi, Alessandro; Menozzi, Marianna; Carli, Federica; Zona, Stefano; Santoro, Antonella; Malagoli, Andrea; Borghi, Vanni; Torricelli, Pietro; Cossarizza, Andrea; Mussini, Cristina
abstract

People with HIV (PWH) may experience accentuating aging in relation to immuno-activation. Little is known regarding thymus (THY) involution in this process. We sought to investigate the relationship between THY imaging detection/size and clinically relevant aging outcomes such as metabolic syndrome (MetS), multimorbidity (MM), and frailty in PWH.

2019 - What is the measure of success in HIV? The fourth 90: quality of life or healthy aging? [Articolo su rivista]
Guaraldi, Giovanni; Milic, Jovana; Wu, Albert W.
abstract

In the short time frame of 30 years, HIV research has been able to modify AIDS from a rapidly progressive disease leading inevitably to death to a chronic condition. Even more, the health status of people living with HIV (PLWH) has significantly improved reducing the burden of symptoms and improving quality of life (QoL). After introduction of the UNAIDS agenda on the “90–90–90 targets”, it remains unclear what should be the next target in HIV care and research. The objective of this paper is to critically discuss potential new outcomes to be used as a measure of success in PLWH both in clinical and research settings. Methods To better portray potential outcomes, we will critically discuss epidemiological and clinical outcomes, patientreported outcomes (PRO), and public health outcomes reported in literature. These outcomes intersect with one another which may suggest contemporary use of different outcomes depending on goals we want to achieve. New outcomes should go beyond undetectability, be patient-centred, and similar to those in geriatric medicine and the general population. Conclusions HIV care can take advantage of experience from geriatric medicine and teach-back by describing aging trajectories in PLWH that may be accentuated in comparison to general population. However, we still need to improve tools to measure quality of life, PROs, and healthy aging. Healthy aging assessment will allow us to recognize unmet needs in PLWH and represents an integrated model between community, the person, and healthcare providers, wherein all stakeholders are linked, increasing possibilities for effective intervention.

2018 - A comprehensive development agenda on tenofovir alafenamide in clinical practice [Articolo su rivista]
Di Biagio, A; Riccardi, N; Rusconi, S; Guaraldi, G; Borderi, M; De Luca, A; Gianotti, N; Lo Caputo, S; Maggi, P; Maserati, R; Maggiolo, F
abstract

The introduction of tenofovir (TFV) alafenamide (TAF) into clinical practice will be a further revolution in antiretroviral therapy. Currently available HIV-1 regimens are wide enough to allow diversified usage in different settings. Despite the fact that TAF is not capillary accessible, even in industrialized countries, ultimate International Guidelines have already included TAF in backbone or in single-tablet regimens. Due to a better safety profile, TAF will progressively replace TFV disoproxil fumarate, both in naïve and experienced patients. However, therapeutic innovations have to deal with budget constraints and different global spending-review patterns. The aim of this article is to give a comprehensive agenda of TAF use in naïve and experienced HIV-1 infected patients, providing a full review of the studies present in the literature and contextualizing these findings into daily clinical practice.

2018 - Abacavir usage patterns and hypersensitivity reactions in the EuroSIDA cohort [Articolo su rivista]
Roen, A.; Laut, K.; Pelchen-Matthews, A.; Borodulina, E.; Caldeira, L.; Clarke, A.; Clotet, B.; d'Arminio Monforte, A.; Fatkenheuer, G.; Gatell Artigas, J. M.; Karpov, I.; Kuznetsova, A.; Kyselyova, G.; Mozer-Lisewska, I.; Mulcahy, F.; Ragone, L.; Scherrer, A.; Uzdaviniene, V.; Vandekerckhove, L.; Vannappagari, V.; Ostergaard, L.; Mocroft, A.; Losso, M.; Kundro, M.; Schmied, B.; Zangerle, R.; Vassilenko, A.; Mitsura, V. M.; Paduto, D.; Clumeck, N.; De Wit, S.; Delforge, M.; Florence, E.; Hadziosmanovic, V.; Begovac, J.; Machala, L.; Jilich, D.; Sedlacek, D.; Kronborg, G.; Benfield, T.; Gerstoft, J.; Katzenstein, T.; Moller, N. F.; Pedersen, C.; Wiese, L.; Nielsen, L. N.; Zilmer, K.; Smidt, J.; Ristola, M.; Aho, I.; Viard, J. -P.; Girard, P. -M.; Pradier, C.; Fontas, E.; Duvivier, C.; Rockstroh, J.; Behrens, G.; Degen, O.; Stellbrink, H. J.; Stefan, C.; Bogner, J.; Chkhartishvili, N.; Gargalianos, P.; Xylomenos, G.; Armenis, K.; Sambatakou, H.; Szlavik, J.; Gottfredsson, M.; Yust, I.; Turner, D.; Burke, M.; Shahar, E.; Hassoun, G.; Elinav, H.; Haouzi, M.; Elbirt, D.; Sthoeger, Z. M.; Esposito, R.; Mazeu, I.; Mussini, C.; Mazzotta, F.; Gabbuti, A.; Vullo, V.; Lichtner, M.; Zaccarelli, M.; Antinori, A.; Acinapura, R.; Plazzi, M.; Lazzarin, A.; Castagna, A.; Gianotti, N.; Galli, M.; Ridolfo, A.; Rozentale, B.; Matulionyte, R.; Staub, T.; Hemmer, R.; Reiss, P.; Reikvam, D. H.; Maeland, A.; Bruun, J.; Knysz, B.; Gasiorowski, J.; Inglot, M.; Horban, A.; Bakowska, E.; Flisiak, R.; Grzeszczuk, A.; Parczewski, M.; Maciejewska, K.; Aksak-Was, B.; Beniowski, M.; Mularska, E.; Smiatacz, T.; Gensing, M.; Jablonowska, E.; Malolepsza, E.; Wojcik, K.; Mansinho, K.; Maltez, F.; Radoi, R.; Oprea, C.; Panteleev, A.; Panteleev, O.; Yakovlev, A.; Trofimora, T.; Khromova, I.; Kuzovatova, E.; Vdoushkina, E.; Jevtovic, D.; Tomazic, J.; Gatell, J. M.; Miro, J. M.; Moreno, S.; Rodriguez, J. M.; Jou, A.; Paredes, R.; Tural, C.; Puig, J.; Bravo, I.; Domingo, P.; Gutierrez, M.; Mateo, G.; Sambeat, M. A.; Laporte, J. M.; Falconer, K.; Thalme, A.; Sonnerborg, A.; Blaxhult, A.; Flamholc, L.; Weber, R.; Cavassini, M.; Calmy, A.; Furrer, H.; Battegay, M.; Schmid, P.; Sluzhynska, M.; Gazzard, B.; Johnson, A. M.; Simons, E.; Edwards, S.; Phillips, A.; Johnson, M. A.; Orkin, C.; Weber, J.; Scullard, G.; Leen, C.; Gatell, J.; Lundgren, J.; Rasmussen, L. D.; Svedhem, V.; Wandeler, G.; Kowalska, J. D.; Miro, J.; Guaraldi, G.; Kirk, O.; Peters, L.; Bojesen, A.; Raben, D.; Kristensen, D.; Larsen, J. F.; Podlekareva, D.; Nykjaer, B.; Cozzi-Lepri, A.; Shepherd, L.; Amele, S.
abstract

Objectives: Five to eight per cent of HIV-positive individuals initiating abacavir (ABC) experience potentially fatal hypersensitivity reactions (HSRs). We sought to describe the proportion of individuals initiating ABC and to describe the incidence and factors associated with HSR among those prescribed ABC. Methods: We calculated the proportion of EuroSIDA individuals receiving ABC-based combination antiretroviral therapy (cART) among those receiving cART after 1 January 2009. Poisson regression was used to identify demographic, and current clinical and laboratory factors associated with ABC utilization and discontinuation. Results: Between 2009 and 2016, of 10 076 individuals receiving cART, 3472 (34%) had ever received ABC-based cART. Temporal trends of ABC utilization were also heterogeneous, with 28% using ABC in 2009, dropping to 26% in 2010 and increasing to 31% in 2016, and varied across regions and over time. Poisson models showed lower ABC utilization in older individuals, and in those with higher CD4 cell counts, higher cART lines, and prior AIDS. Higher ABC utilization was associated with higher HIV RNA and poor renal function, and was more common in Central-East and Eastern Europe and lowest during 2014. During 779 person-years of follow-up (PYFU) in 2139 individuals starting ABC after 1 January 2009, 113 discontinued ABC within 6 weeks of initiation for any reason [incidence rate (IR) 14.5 (95% confidence interval (CI) 12.1, 17.5) per 100 PYFU], 13 because of reported HSR [IR 0.3 (95% CI 0.1, 1.0) per 100 PYFU] and 35 because of reported HSR/any toxicity [IR 4.5 (95% CI 3.2, 6.3) per 100 PYFU]. There were no factors significantly associated with ABC discontinuation because of reported HSR/any toxicity. Conclusions: ABC remains commonly used across Europe and the incidence of discontinuation because of reported HSR was low in our study population.

2018 - Abacavir/Lamivudine and Tenofovir/Emtricitabine in Pregnant Women with Hiv: Laboratory and Clinical Outcomes in an Observational National Study [Articolo su rivista]
Floridia, Marco; Pinnetti, Carmela; Ravizza, Marina; Masuelli, Giulia; Personeni, Carlo; Sansone, Matilde; Antoni, Anna Degli; Guaraldi, Giovanni; Spinillo, Arsenio; Tassis, Beatrice; Dalzero, Serena; Liuzzi, Giuseppina; Tamburrini, Enrica
abstract

Abacavir-lamivudine (ABC/3TC) and tenofovir-emtricitabine (TDF/FTC) represent in the guidelines of several countries, including Italy and United States, the preferred nucleoside/nucleotide backbones of antiretroviral regimens. We assessed their profile in pregnancy using data from a national observational study.

2018 - Atazanavir and darunavir in pregnant women with HIV: Evaluation of laboratory and clinical outcomes from an observational national study [Articolo su rivista]
Floridia, M.; Masuelli, G.; Ravizza, M.; Tassis, B.; Cetin, I.; Sansone, M.; Antoni, A. D.; Simonazzi, G.; Maccabruni, A.; Francisci, D.; Frisina, V.; Liuzzi, G.; Dalzero, S.; Tamburrini, E.; Di Lorenzo, F.; Sterrantino, G.; Meli, M.; Campolmi, I.; Vichi, F.; Del Pin, B.; Marocco, R.; Mastroianni, C.; S. Mercurio, V.; Zanaboni, D.; Guaraldi, G.; Nardini, G.; Stentarelli, C.; Beghetto, B.; Antoni, A. M. D.; Molinari, A.; Crisalli, M. P.; Donisi, A.; Piepoli, M.; Cerri, V.; Zuccotti, G.; Giacomet, V.; Coletto, S.; Di Nello, F.; Madia, C.; Placido, G.; Milini, P.; Savalli, F.; Portelli, V.; Sabbatini, F.; Papalini, C.; Bernini, L.; Grossi, P.; Rizzi, L.; Bernardon, M.; Maso, G.; Rizzante, E.; Belcaro, C.; Meloni, A.; Dedoni, M.; Ortu, F.; Piano, P.; Citernesi, A.; Bordonivicini, I.; Luzi, K.; Spinillo, A.; Roccio, M.; Vimercati, A.; Crupano, F. M.; Calabretti, D.; Cervi, F.; Margarito, E.; Capretti, M. G.; Marsico, C.; Faldella, G.; Martinelli, P.; Agangi, A.; Capone, A.; Maruotti, G. M.; Tibaldi, C.; Trentini, L.; Todros, T.; Brambilla, T.; Savasi, V.; Personeni, C.; Giaquinto, C.; Fiscon, M.; Rubino, E.; Franceschetti, L.; Badolato, R.; Tiso, G. C.; Genovese, O.; Cafforio, C.; Pinnetti, C.; Casadei, A. M.; Cavaliere, A. F.; Cellini, M.; Marconi, A. M.; Sacchi, V.; Ierardi, M.; Polizzi, C.; Mattei, A.; Pirillo, M. F.; Amici, R.; Galluzzo, C. M.; Donnini, S.; Baroncelli, S.; Villani, P.; Cusato, M.; Cerioli, A.; De Martino, M.; Parazzini, F.; Vella, S.
abstract

Background: Atazanavir and darunavir represent the main HIV PIs recommended in pregnancy, but comparativedata in pregnant women are limited.We assessed the safety and activity profile of these two drugs in pregnancyusing data from a national observational study.Methods: Women with atazanavir or darunavir exposure in pregnancy were evaluated for laboratory measuresand main pregnancy outcomes (e.g. preterm delivery, low birthweight, non-elective caesarean section and neonatalgestational age-adjusted birthweight Z-score).Results: Final analysis included 500 pregnancies with either atazanavir (n"409) or darunavir (n"91) exposure.No differences in pregnancy outcomes, weight gain in pregnancy, drug discontinuations, undetectable HIV-RNA,haemoglobin, ALT, total cholesterol, HDL cholesterol and LDL cholesterol were observed between the twogroups. At third trimester, exposure to darunavir was associated with higher levels of plasma triglycerides(median 235.5 versus 179 mg/dL; P"0.032) and a higher total cholesterol/HDL cholesterol ratio (median 4.03versus 3.27; P"0.028) and exposure to atazanavir was associated with higher levels of plasma bilirubin (1.54versus 0.32 mg/dL; P&lt;0.001).Conclusions: In this observational study, the two main HIV PIs currently recommended by perinatal guidelinesshowed similar safety and activity in pregnancy, with no evidence of differences between the two drugs in termsof main pregnancy outcomes. Based on the minor differences observed in laboratory measures, prescribingphysicians might prefer either drug in some particular situations where the different impacts of treatment onlipid profile and bilirubin may have clinical relevance.

2018 - Bone Mineral Density Declines Twice as Quickly Among HIV-Infected Women Compared to Men [Articolo su rivista]
Erlandson, Kristine M; Lake, Jordan E; Sim, Myung; Falutz, Julian; Prado, Carla M; Domingues Da Silva, Ana Rita; Brown, Todd T; Guaraldi, Giovanni
abstract

Initial declines in bone mineral density (BMD) following antiretroviral therapy (ART) initiation in HIV are well described, but data on long-term changes and risk factors for decline, particularly among women, are limited.

2018 - Chronic Lung Disease in HIV Patients [Articolo su rivista]
Neri, S; Leung, J; Besutti, G; Santoro, A; Fabbri, Lm; Guaraldi, G
abstract

This narrative review discusses literature on chronic obstructive pulmonary disease (COPD) in people living with HIV (PLWH). Existing data indicate that HIV itself, independent of smoking, constitutes a pathogenic agent implicated in this disease condition. COPD can be viewed not exclusively as a pulmonary disease but rather as a systemic syndrome sparked and fueled by a persistent low-grade HIV-attributable inflammatory state. We speculate that even in the absence of airflow obstruction on spirometry, HIV-related lung disease can manifest with respiratory symptoms and structural lung derangement. Although not fully satisfying the global initiative for obstructive lung disease criteria for COPD, this phenotype of small airways lung disease is related to significant impairment of lung health and is associated with a high comorbidity burden. Within the specific context of the aging epidemic affecting HIV patients characterized by a high burden of comorbidities, frailty, and disabilities HIV-related lung disease has to be fit into the framework of the general comorbidity burden that PLWH experience, due to both HIV infection and to incidental HIV-unrelated risk factors. In this review, we will also provide a list of research gaps and an agenda for future studies in HIV patients.

2018 - Construct validation of a Frailty Index, an HIV Index and a Protective Index from a clinical HIV database [Articolo su rivista]
Franconi, Iacopo; Theou, Olga; Wallace, Lindsay; Malagoli, Andrea; Mussini, Cristina; Rockwood, Kenneth; Guaraldi, Giovanni
abstract

Standard care for HIV clinical practice has started focusing on age-related problems, but despite this recent change physicians involved in HIV care do not often screen HIV patients for frailty. Our aim was to construct three indexes from an HIV clinical database (i.e. Frailty Index, (FI), HIV Index, (HIVI), and Protective Index (PI)) and to assess levels of frailty, HIV severity and demographic and protective lifestyle factors among HIV patients. Methods and findings We included data from 1612 patients who attended an Italian HIV clinic between September 2016 and December2017 (mean±SD age: 53.1±8 years, 73.9% men).We used 92 routine variables collected by physicians and other health care professionals to construct three indexes: A 72-item FI (biometric, psychiatric, blood test, daily life activities, geriatric syndromes and nutrition data), a 10-item HIVI (immunological, viral and therapeutics) and a 10-item PI (income, education, social engagement, and lifestyle habits data)(the lower the FI and HIVI scores, and the higher the PI scores, the lower the risk for participants).The FI, HIVI and PI scores were 0.19±0.08, 0.48±0.17 and 0.62±0.13, respectively. Men had higher FI (0.19±0.08 vs 0.18±0.08; p = 0.010) and lower HIVI (0.47±0.18 vs 0.50±0.15; p = 0.038) scores than women. FI and HIVI scores both increased 1.9% per year of age (p &lt; 0.001), whereas the PI decreased 0.2% per year (p&lt;0.050). In addition, the FI score increased 1.6% and the PI score decreased 0.5% per year of HIV infection (p &lt; 0.001). Conclusion It is feasible to assess levels of frailty, HIV severity and protective lifestyle factors in HIV patients using data from a clinical database. Frailty levels are high among HIV patients and even higher among older patients and those with a long duration of HIV. Future studies need to examine the ability of the three indices to predict adverse health outcomes such as hospitalization and mortality.

2018 - Erratum: Role of tenofovir alafenamide in the jungle of antiretroviral prescription [J Antimicrob Chemother, 73, (2018), (261-262)] DOI: 10.1093/jac/dkx346 [Articolo su rivista]
Guaraldi, G.
abstract

In the fifth paragraph of the original published version of this article the third sentence was incorrect. The correct sentence is: Fromthis perspective, the impact of tenofovir alafenamide in the HIV treatment armamentarium goes beyond its capacity to reduce drug toxicities. This error has nowbeen corrected.

2018 - First-line antiretroviral therapy with efavirenz plus tenofovir disiproxil fumarate/emtricitabine or rilpivirine plus tenofovir disiproxil fumarate/emtricitabine: a durability comparison [Articolo su rivista]
Taramasso, L.; Di Biagio, A.; Maggiolo, F.; Tavelli, A.; Lo Caputo, S.; Bonora, S.; Zaccarelli, M.; Caramello, P.; Costantini, A.; Viscoli, C.; d'Arminio Monforte, A.; Cozzi-Lepri, A.; Andreoni, M.; Angarano, G.; Antinori, A.; Castelli, F.; Cauda, R.; Di Perri, G.; Galli, M.; Iardino, R.; Ippolito, G.; Lazzarin, A.; Perno, C. F.; von Schloesser, F.; Viale, P.; Castagna, A.; Ceccherini-Silberstein, F.; Girardi, E.; Mussini, C.; Puoti, M.; Ammassari, A.; Balotta, C.; Bandera, A.; Bonfanti, P.; Borderi, M.; Calcagno, A.; Calza, L.; Capobianchi, M. R.; Cingolani, A.; Cinque, P.; De Luca, A.; Gianotti, N.; Gori, A.; Guaraldi, G.; Lapadula, G.; Lichtner, M.; Madeddu, G.; Marchetti, G.; Marcotullio, S.; Monno, L.; Nozza, S.; Quiros Roldan, E.; Rossotti, R.; Rusconi, S.; Santoro, M. M.; Saracino, A.; Fanti, I.; Galli, L.; Lorenzini, P.; Rodano, A.; Shanyinde, M.; Carletti, F.; Carrara, S.; Di Caro, A.; Graziano, S.; Petrone, F.; Prota, G.; Quartu, S.; Truffa, S.; Giacometti, A.; Valeriani, C.; Santoro, C.; Suardi, C.; Donati, V.; Verucchi, G.; Minardi, C.; Quirino, T.; Abeli, C.; Manconi, P. E.; Piano, P.; Cacopardo, B.; Celesia, B.; Vecchiet, J.; Falasca, K.; Sighinolfi, L.; Segala, D.; Mazzotta, F.; Vichi, F.; Cassola, G.; Alessandrini, A.; Bobbio, N.; Mazzarello, G.; Mastroianni, C.; Belvisi, V.; Caramma, I.; Chiodera, A.; Castelli, A. P.; Rizzardini, G.; Ridolfo, A. L.; Piolini, R.; Salpietro, S.; Carenzi, L.; Moioli, M. C.; Tincati, C.; Puzzolante, C.; Abrescia, N.; Chirianni, A.; Borgia, G.; Di Martino, F.; Maddaloni, L.; Gentile, I.; Orlando, R.; Baldelli, F.; Francisci, D.; Parruti, G.; Ursini, T.; Magnani, G.; Ursitti, M. A.; Vullo, V.; Cristaudo, A.; Baldin, G.; Cicalini, S.; Gallo, L.; Nicastri, E.; Acinapura, R.; Capozzi, M.; Libertone, R.; Savinelli, S.; Latini, A.; Cecchetto, M.; Viviani, F.; Mura, M. S.; Rossetti, B.; Orofino, G. C.; Sciandra, M.; Bassetti, M.; Londero, A.; Pellizzer, G.; Manfrin, V.
abstract

Objectives: The aim of this study was to compare the durabilities of efavirenz (EFV) and rilpivirine (RPV) in combination with tenofovir/emtricitabine (TDF/FTC) in first-line regimens. Methods: A multicentre prospective and observational study was carried out. We included all patients participating in the Italian Cohort Naive Antiretrovirals (ICONA) Foundation Study who started first-line combination antiretroviral therapy (cART) with TDF/FTC in combination with RPV or EFV, with a baseline viral load &lt; 100 000 HIV-1 RNA copies/mL. Survival analyses using Kaplan–Meier (KM) curves and Cox regression with time-fixed covariates at baseline were employed. Results: Overall, 1490 ART-naïve patients were included in the study, of whom 704 were initiating their first cART with EFV and 786 with RPV. Patients treated with EFV, compared with those on RPV, were older [median 36 (interquartile range (IQR) 30–43) years vs. 33 (IQR 27–39) years, respectively; P &lt; 0.001], were more frequently at Centers for Disease Control and Prevention (CDC) stage C (3.1% vs. 1.4%, respectively; P = 0.024), and had a lower median baseline CD4 count [340 (IQR 257–421) cells/μL vs. 447 (IQR 347–580) cells/μL, respectively; P &lt; 0.001] and a higher median viral load [4.38 (IQR 3.92–4.74) log10 copies/mL vs. 4.23 (IQR 3.81–4.59) log10 copies/mL, respectively], (P = 0.004). A total of 343 patients discontinued at least one drug of those included in the first cART regimen, more often EFV (26%) than RPV (13%), by 2 years (P &lt; 0.0001). After adjustment, patients treated with EFV were more likely to discontinue at least one drug for any cause [relative hazard (RH) 4.09; 95% confidence interval (CI) 2.89–5.80], for toxicity (RH 2.23; 95% CI 1.05–4.73) for intolerance (RH 5.17; 95% CI 2.66–10.07) and for proactive switch (RH 10.96; 95% CI 3.17–37.87) than those starting RPV. Conclusions: In our nonrandomized comparison, RPV was better tolerated, less toxic and showed longer durability than EFV, without a significant difference in rates of discontinuation because of failures.

2018 - Gastric Mucormycosis in a Liver and Kidney Transplant Recipient: Case Report and Concise Review of Literature [Articolo su rivista]
Alfano, G.; Fontana, F.; Francesca, D.; Assirati, Giacomo; Magistri, P.; Tarantino, G.; Ballarin, R.; Rossi, G.; Franceschini, E.; Codeluppi, M.; Guaraldi, G.; Mussini, C.; Di Benedetto, F.; Cappelli, G.
abstract

Mucormycosis is an uncommonly encountered fungal infection in solid organ transplantation. The infection is severe and often results in a fatal outcome. The most common presentations are rhino-sino-orbital and pulmonary disease. We describe a rare case of gastric mucormycosis in a patient with a combined liver-kidney transplant affected by glycogen storage disease type Ia. A 42-year-old female patient presented with gastric pain and melena 26 days after transplantation. Evaluation with upper endoscopy showed two bleeding gastric ulcers. Histological examination of gastric specimens revealed fungal hyphae with evidence of Mucormycetes at subsequent molecular analysis. Immunosuppressive therapy was reduced and antifungal therapy consisting of liposomal amphotericin B and posaconazole was promptly introduced. Gastrointestinal side effects of posaconazole and acute T-cell rejection of renal graft complicated further management of the case. A prolonged course of daily injections of amphotericin B together with a slight increase of immunosuppression favored successful treatment of mucormycosis as well as of graft rejection. After 2-year follow-up examination, the woman was found to have maintained normal renal and liver function tests. We conclude that judicious personalization of antimicrobial and antirejection therapy should be considered to resolve every life-threatening case of mucormycosis in solid organ transplantation.

2018 - Gonadal function in human immunodeficiency virus (HIV)-infected men assessed by isotopic dilution-liquid chromatography-tandem mass spectrometry (ID-LC-MS/MS) and chemiluminescent assay. [Abstract in Atti di Convegno]
De Vincentis, S.; Decaroli, M. C.; Diazzi, C.; Morini, F.; Bertani, D.; Fanelli, F.; Mezzullo, M.; Santi, D.; Baraldi, E.; Tagliavini, S.; Pagotto, U.; Guaraldi, G.; Rochira, Vincenzo
abstract

BACKGROUND: HIV infection is associated to premature decline of serum T1,2. However, prevalence and biochemical characterization of hypogonadism in HIV-infected men are still to be well defined1,2. AIM OF THE STUDY: We evaluated the gonadal status in young to middle aged HIV-infected men in order to characterize hypogonadism by assessing circulating total T (TT) with either Liquid Chromatography tandem Mass Spectrometry (LC-MS/MS) or chemiluminescent immunoassay. METHODS: Prospective, cross-sectional, observational study on 315 consecutive HIV-infected male patients with ongoing Highly Active Antiretroviral Therapy (HAART), attending the Metabolic Clinic of Infectious Diseases. Serum TT, gonadotropins and sex hormone-binding globulin (SHBG) were measured by chemiluminescent immunoassay. Serum TT was also assessed by the gold standard LC-MS/MS in 233 patients. Free T (FT) was calculated by using Vermeulen equation3. Hypogonadism was defined as serum TT levels below 320 ng/dL and/or free T levels below 64 pg/ml4. Statistical analysis: Categorical variables were compared using Chi-Square test, while correlations were performed using Spearman’s Rho coefficient and linear regression models. RESULTS: 315 HIV-infected patients were enrolled (mean age 45.56±5.61 years) with average duration of HIV-infection of 16.57±10.45 years. Considering serum total T levels assessed by LC-MS/MS and immunoassay, 11 patients out of 233 (4.8%) and 10 patients out of 315 (3.2%) had T deficiency, respectively. TT combined with luteinizing hormone (LH) levels was used to classify hypogonadism (Table 1). No difference was found among subgroups comparing the two methodologies used for TT measurement (p=0.914). 56 patients (17.8%) showed SHBG above the normal range (>71.4 nmol/L). Considering calculated FT, the incidence of hypogonadism raised to 6.9% using either immunoassay or LC-MS/MS, respectively (Table 1), with no difference between methodologies (p=0.895). Including compensated form oh hypogonadism, the prevalence raised to 13% for TT and to 15% for FT. Patients with low FT were older than eugonadal patients (p=0.005) and showed a significantly longer duration of HIV-infection (p<0.0001) and HAART (p=0.002), while they did not differ for body mass index (p=0.231). FT showed an inverse relation with age (-0.340, p<0.0001, R2=0.116), years of infection (-0.339, p<0.0001, R2=0.120) and years of HAART (-0.346, p<0.0001, R2=0.117), but not with BMI of patients. CONCLUSIONS: To the best of our knowledge, this is the first, properly-designed prospective study aiming to investigate the gonadal status of HIV-infected men with both LC-MS/MS and chemiluminescent assay. In HIV-infected patients a) the two methodologies have equivalent reliability in TT measurement; b) SHBG for calculated FT is essential for the detection of T deficiency, revealing the real prevalence of hypogonadism in this context; c) duration of HIV-infection and HAART seem to be potent predictive factors for serum FT levels, suggesting a concomitant negative effect of virus per se and antiretroviral drugs on gonadal function. References 1Rochira V et al. Premature decline of serum total testosterone in HIV-infected men in the HAART-era. PLoS One. 2011;6(12):e28512. 2Rochira V & Guaraldi G. Hypogonadism in the HIV-infected man. Endocrinol Metab Clin North Am. 2014 Sep;43(3):709-30. 3Vermeulen A et al. A critical evaluation of simple methods for the estimation of free testosterone in serum. J Clin Endocrinol Metab 1999; 84:3666–3672 4Bhasin S et al. Testosterone Therapy in Men With Hypogonadism: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2018 May 1;103(5):1715-1744.

2018 - Highlights of the 2017 European AIDS Clinical Society (EACS) Guidelines for the treatment of adult HIV-positive persons version 9.0 [Articolo su rivista]
Ryom, L.; Boesecke, C.; Bracchi, M.; Ambrosioni, J.; Pozniak, A.; Arribas, J.; Behrens, G.; Mallon, P. G. M.; Puoti, M.; Rauch, A.; Miro, J. M.; Kirk, O.; Marzolini, C.; Lundgren, J. D.; Battegay, M.; d'Arminio Monforte, A.; Clumeck, N.; Dedes, N.; Gatell, J. M.; Horban, A.; Katlama, C.; McCormack, S.; Molina, J. -M.; Mussini, C.; Raffi, F.; Reiss, P.; Stellbrink, H. -J.; Bower, M.; Cinque, P.; Collins, S.; Compston, J.; De Wit, S.; Fabbri, L. M.; Fux, C. A.; Guaraldi, G.; Martinez, E.; Papapoulos, S.; du Pasquier, R.; Poulter, N.; Williams, I.; Winston, A.; Berenguer, J.; Bhagani, S.; Bruno, R.; Konov, S.; Lacombe, K.; Mauss, S.; Mendao, L.; Peters, L.; Rockstroh, J. K.; Fatkenheuer, G.; Furrer, H.; Mocroft, A.; Morlat, P.; Volny-Anne, A.
abstract

Background: The European AIDS Clinical Society (EACS) Guidelines have since 2005 provided multidisciplinary recommendations for the care of HIV-positive persons in geographically diverse areas. Guideline highlights: Major revisions have been made in all sections of the 2017 Guidelines: antiretroviral treatment (ART), comorbidities, coinfections and opportunistic diseases. Newly added are also a summary of the main changes made, and direct video links to the EACS online course on HIV Management. Recommendations on the clinical situations in which tenofovir alafenamide may be considered over tenofovir disoproxil fumarate are provided, and recommendations on which antiretrovirals can be used safely during pregnancy have been revised. Renal and bone toxicity and hepatitis C virus (HCV) treatment have been added as potential reasons for ART switches in fully virologically suppressed individuals, and dolutegravir/rilpivirine has been included as a treatment option. In contrast, dolutegravir monotherapy is not recommended. New recommendations on non-alcoholic fatty liver disease, chronic lung disease, solid organ transplantation, and prescribing in elderly are included, and human papilloma virus (HPV) vaccination recommendations have been expanded. All drug–drug interaction tables have been updated and new tables are included. Treatment options for direct-acting antivirals (DAAs) have been updated and include the latest combinations of sofosbuvir/velpatasvir/voxilaprevir and glecaprevir/pibrentasvir. Recommendations on management of DAA failure and acute HCV infection have been expanded. For treatment of tuberculosis (TB), it is underlined that intermittent treatment is contraindicated, and for resistant TB new data suggest that using a three-drug combination may be as effective as a five-drug regimen, and may reduce treatment duration from 18-24 to 6-10&nbsp;months. Conclusions: Version 9.0 of the EACS Guidelines provides a holistic approach to HIV care and is translated into the six most commonly spoken languages.

2018 - IL SODIO SIERICO È INVERSAMENTE CORRELATO ALLA FRAILTY E ALLA DENSITÀ MINERALE OSSEA (BMD) NEI PAZIENTI CON INFEZIONE DA HUMAN IMMUNODEFICIENCY VIRUS (HIV) [Abstract in Atti di Convegno]
De Vincentis, S.; Decaroli, MARIA CHIARA; Diazzi, C.; Santi, D.; Menozzi, M.; Zona, S.; Guaraldi, G.; Rochira, V.
abstract

L'iponatriemia si associa alla frailty nei pazienti con infezione da HIV

2018 - Immunophenotypic Profile and Clinical Outcome of Monoclonal B-cell Lymphocytosis in Kidney Transplantation [Articolo su rivista]
Alfano, G; Fontana, F; Colaci, E; Franceschini, E; Ligabue, G; Messerotti, A; Bettelli, Francesca; Grottola, A; Gennari, W; Potenza, L; Guaraldi, G; Mussini, C; Luppi, M; Cappelli, G
abstract

Monoclonal B-cell lymphocytosis (MBL) is a lymphoproliferative disorder characterized by clonal expansion of a B-cell population in peripheral blood of otherwise healthy subjects. MBL is divided into CLL (chronic lymphocytic leukemia)-like, atypical CLL-like and non-CLL MBL. The aim of this study was to evaluate immunophenotypic characteristics and clinical outcomes of MBL in kidney transplant (KT) recipients. We retrospectively evaluated 593 kidney transplant (KT) recipients in follow-up at our center. Among them, 157 patients underwent peripheral blood flow-cytometry for different clinical indications. A 6-color panel flow-cytometry was used to diagnose MBL. MBL was detected in 5 of 157 KT recipients. Immunophenotypic characterization of MBL showed four cases of non-CLL MBL and one case of CLL-like MBL. At presentation, median age was 65 years (range 61-73). After a median follow-up of 3.1 years (95%CI; 1.1-5) from diagnosis, patients did not progress either to CLL or lymphoma. The disorder did not increase the risk of malignancy, severe infections, graft loss and mortality among our KT recipients. Surprisingly, all cases were also affected by concomitant monoclonal gammopathy of undetermined significance, which did not progress to multiple myeloma during follow-up. In conclusion, our data suggest that MBL is an age-related disorder, with non-CLL MBL being the most common subtype among KT recipients. This article is protected by copyright. All rights reserved.

2018 - Impact of social determinants on antiretroviral therapy access and outcomes entering the era of universal treatment for people living with HIV in Italy [Articolo su rivista]
Saracino, A.; Zaccarelli, M.; Lorenzini, P.; Bandera, Alessandra; Marchetti, G.; Castelli, F.; Gori, A.; Girardi, E.; Mussini, C.; Bonfanti, P.; Ammassari, A.; D'Arminio Monforte, A.; Moroni, M.; Andreoni, M.; Angarano, G.; Antinori, A.; Cauda, R.; Di Perri, G.; Galli, M.; Iardino, R.; Ippolito, G.; Lazzarin, A.; Perno, C. F.; Von Schloesser, F.; Viale, P.; Castagna, A.; Ceccherini-Silberstein, F.; Cozzi-Lepri, A.; Lo Caputo, S.; Puoti, M.; Balotta, C.; Bonora, S.; Borderi, M.; Capobianchi, M. R.; Cingolani, A.; Cinque, P.; De Luca, A.; Di Biagio, A.; Gianotti, N.; Guaraldi, G.; Lapadula, G.; Lichtner, M.; Madeddu, G.; Maggiolo, F.; Marcotullio, S.; Monno, L.; Quiros Roldan, E.; Rusconi, S.; Cicconi, P.; Fanti, I.; Galli, L.; Shanyinda, M.; Tavelli, A.; Giacometti, A.; Costantini, A.; Mazzoccato, S.; Santoro, C.; Suardi, C.; Vanino, E.; Verucchi, G.; Minardi, C.; Quirino, T.; Abeli, C.; Manconi, P. E.; Piano, P.; Vecchiet, J.; Falasca, K.; Sighinolfi, L.; Segala, D.; Mazzotta, F.; Cassola, G.; Viscoli, C.; Alessandrini, A.; Piscopo, R.; Mazzarello, G.; Mastroianni, C.; Belvisi, V.; Caramma, I.; Chiodera, A.; Castelli, A. P.; Rizzardini, G.; Ridolfo, A. L.; Piolini, R.; Salpietro, S.; Carenzi, L.; Moioli, M. C.; Tincati, C.; Puzzolante, C.; Abrescia, N.; Chirianni, A.; Borgia, G.; Guida, M. G.; Gargiulo, M.; Gentile, I.; Orlando, R.; Baldelli, F.; Francisci, D.; Parruti, G.; Ursini, T.; Magnani, G.; Ursitti, M. A.; Vullo, V.; D'Avino, A.; Gallo, L.; Nicastri, E.; Acinapura, R.; Capozzi, M.; Libertone, R.; Tebano, G.; Viviani, F.; Sasset, L.; Mura, M. S.; Rossetti, B.; Caramello, P.; Orofino, G. C.; Sciandra, M.; Bassetti, M.; Londero, A.; Pellizzer, G.; Manfrin, V.
abstract

Background: Social determinants are known to be a driving force of health inequalities, even in high income countries. Aim of our study was to determine if these factors can limit antiretroviral therapy (ART) access, outcome and retention in care of people living with HIV (PLHIV) in Italy. Methods: All ART naïve HIV+ patients (pts) of Italian nationality enrolled in the ICONA Cohort from 2002 to 2016 were included. The association of socio-demographic characteristics (age, sex, risk factor for HIV infection, educational level, occupational status and residency area) with time to: ART initiation (from the first positive anti-HIV test), ART regimen discontinuation, and first HIV-RNA < 50 cp/mL, were evaluated by Cox regression analysis, Kaplan Meier method and log-rank test. Results: A total of 8023 HIV+ pts (82% males, median age at first pos anti-HIV test 36 years, IQR: 29-44) were included: 6214 (77.5%) started ART during the study period. Women, people who inject drugs (PWID) and residents in Southern Italy presented the lowest levels of education and the highest rate of unemployment compared to other groups. Females, pts aged > 50 yrs., unemployed vs employed, and people with lower educational levels presented the lowest CD4 count at ART initiation compared to other groups. The overall median time to ART initiation was 0.6 years (yrs) (IQR 0.1-3.7), with a significant decrease over time [2002-2006 = 3.3 yrs. (0.2-9.4); 2007-2011 = 1.0 yrs. (0.1-3.9); 2012-2016 = 0.2 yrs. (0.1-2.1), p < 0.001]. By multivariate analysis, females (p < 0.01) and PWID (p < 0.001), presented a longer time to ART initiation, while older people (p < 0.001), people with higher educational levels (p < 0.001), unemployed (p = 0.02) and students (p < 0.001) were more likely to initiate ART. Moreover, PWID, unemployed vs stable employed, and pts. with lower educational levels showed a lower 1-year probability of achieving HIV-RNA suppression, while females, older patients, men who have sex with men (MSM), unemployed had higher 1-year risk of first-line ART discontinuation. Conclusions: Despite median time to ART start decreased from 2002 to 2016, socio-demographic factors still contribute to disparities in ART initiation, outcome and durability.

2018 - Incidence of HCV infection amongst HIV positive men who had sex with men and prevalence data from patients followed at the Infectious Diseases Clinic of Modena, Italy [Articolo su rivista]
Cuomo, Gianluca; Digaetano, Margherita; Menozzi, Marianna; Tagliazucchi, Sara; Guaraldi, Giovanni; Borghi, Vanni; Mussini, Cristina
abstract

Background: Men who had sex with men (MSM) living with HIV are at higher risk of developing sexual transmitted diseases. This study reports two years incidence rate and prevalence of HCV in a cohort of HIV positive MSM. Methods: MSM HIV-positive outpatients negative to HCV-Ab at first observation entered a Kaplan–Meier model in order to assess the HCV infection incidence rate. Prevalence analysis was performed with MSM HIV-positive that were on follow-up at 2016. An MSM population HIV-negative served as control. Results: 421 patients entered the incidence analysis. The incidence rate of HCV infection among MSM-HIV people was 0.44 per 100 patients-years (19 events). 40 out of 442 (9%) patients were HCV-positive (prevalence analysis); they were mostly genotype 1a and 3 with APRI score &lt;0.7 (87.5%). Univariate analysis between MSM HIV-positive patients and MSM HIV-negative showed significant differences in the prevalence rate (9.0% vs 0.6%, P &lt; 0.001) and median age (39 vs 47, P &lt; 0.001). Conclusion: Incidence and prevalence rate of HCV amongst MSM HIV-positive patients is higher than in other settings. Annual HCV-Ab screening for MSM HIV-positive patients should be enforced and early treatment of HCV recommended.

2018 - Managing antiretroviral therapy in the elderly HIV patient [Articolo su rivista]
Guaraldi, Giovanni; Pintassilgo, Ines; Milic, Jovana; Mussini, Cristina
abstract

Owing to more effective and less toxic antiretroviral therapy (ART), people living with HIV (PLWH) live longer, a phenomenon expected to grow in the next decades. With advancing age, effectively treated PLWH experience not only a heightened risk for non-infective comorbidities and multimorbidity, but also for geriatric syndromes and frailty. In addition, older adults living with HIV (OALWH) have a higher prevalence of so-called iatrogenic triad described as polypharmacy (PP), potentially inappropriate medication use, and drug-drug interactions. Areas covered: This review will focus the management of ART in OALWH. We will discuss iatrogenic triad and best way to address PP. Special focus will be given to pharmacokinetic and pharmacodynamic aspects of ART in the elderly, evaluation of ART toxicities, and specific ART strategies commonly used in this population. Expert commentary: Research should be focused on recruiting more OALWH, frail individuals in particular, into the clinical trials and specific geriatric outcome need to be considered together with traditional viroimmunological outcomes.

2018 - Pre-ART HIV-1 DNA in CD4+ T cells correlates with baseline VIRO-immunological status and outcome in patients under first-line ART [Articolo su rivista]
Ceccherini-Silberstein, F.; Cozzi Lepri, A.; Alteri, C.; Merlini, E.; Surdo, M.; Marchetti, G.; Capobianchi, M. R.; De Luca, A.; Gianotti, N.; Viale, P.; Andreoni, M.; Antinori, A.; Perno, C. F.; D'Arminio Monforte, A.; Castagna, A.; Castelli, F.; Cauda, R.; Di Perri, G.; Galli, M.; Iardino, R.; Ippolito, G.; Lazzarin, A.; Marchetti, G. C.; Rezza, G.; Von Schloesser, F.; Cozzi-Lepri, A.; Girardi, E.; Lo Caputo, S.; Mussini, C.; Puoti, M.; Ammassari, A.; Balotta, C.; Bandera, A.; Bonfanti, P.; Bonora, S.; Borderi, M.; Calcagno, A.; Calza, L.; Cingolani, A.; Cinque, P.; Di Biagio, A.; Gori, A.; Guaraldi, G.; Lapadula, G.; Lichtner, M.; Madeddu, G.; Maggiolo, F.; Marcotullio, S.; Monno, L.; Nozza, S.; Quiros Roldan, E.; Rossotti, R.; Rusconi, S.; Santoro, M. M.; Saracino, A.; Zaccarelli, M.; Fanti, I.; Galli, L.; Lorenzini, P.; Rodano, A.; Shanyinde, M.; Tavelli, A.; Carletti, F.; Carrara, S.; Di Caro, A.; Graziano, S.; Petrone, F.; Prota, G.; Quartu, S.; Truffa, S.; Giacometti, A.; Costantini, A.; Barocci, V.; Angarano, G.; Santoro, C.; Suardi, C.; Donati, V.; Verucchi, G.; Minardi, C.; Quirino, T.; Abeli, C.; Manconi, P. E.; Piano, P.; Cacopardo, B.; Celesia, B.; Vecchiet, J.; Falasca, K.; Sighinolfi, L.; Segala, D.; Blanc, P.; Vichi, F.; Cassola, G.; Viscoli, C.; Alessandrini, A.; Bobbio, N.; Mazzarello, G.; Mastroianni, C.; Pozzetto, I.; Molteni, C.; Chiodera, A.; Milini, P.; Nunnari, G.; Pellicano, G.; Rizzardini, G.; Moioli, M. C.; Piolini, R.; Ridolfo, A. L.; Salpietro, S.; Tincati, C.; Puzzolante, C.; Chirianni, A.; Borgia, G.; Esposito, V.; Orlando, R.; Bonadies, G.; Di Martino, F.; Gentile, I.; Maddaloni, L.; Cattelan, A. M.; Marinello, S.; Cascio, A.; Colomba, C.; Baldelli, F.; Schiaroli, E.; Parruti, G.; Sozio, F.; Magnani, G.; Ursitti, M. A.; Acinapura, R.; Baldin, G.; Capozzi, M.; Cicalini, S.; Cristaudo, A.; Fontanelli Sulekova, L.; Iaiani, G.; Latini, A.; Mastrorosa, I.; Plazzi, M. M.; Savinelli, S.; Vergori, A.; Vullo, V.; Cecchetto, M.; Viviani, F.; Bagella, P.; Rossetti, B.; Franco, A.; Fontana Del Vecchio, R.; Francisci, D.; Di Giuli, C.; Caramello, P.; Orofino, G. C.; Sciandra, M.; Bassetti, M.; Londero, A.; Pellizzer, G.; Manfrin, V.; Starnini, G.; Ialungo, A.
abstract

Objectives We evaluated the association between pre-ART HIV DNA and HIV-infected participant characteristics at baseline as well as with their response to first-line ART. Methods Four hundred and thirty-three patients from the ICONA cohort, starting first-line ART after the year 2000, were analysed. Pre-ART HIV DNA was quantified with the modified COBAS TaqMan HIV-1 Test and normalized by CD4+ T cells. Linear correlation between pre-ART HIV DNA and other continuous markers (HIV RNA, CD4 count, markers of inflammation and coagulation) at baseline was evaluated by means of Pearson correlation coefficient and a linear regression model. Survival analyses and Cox regression models were used to study the association between pre-ART HIV DNA and time to VIRO-immunoclinical events. Results Pre-ART HIV DNA [median (IQR): 10 € 702 (3397-36 € 632) copies/10 6 CD4+ T cells] was correlated with pre-ART HIV RNA [R 2 = +0.44, (P &lt; 0.0001)], CD4+ T cells [R 2 = '0.58, (P &lt; 0.0001)] and CD4/CD8 ratio [R 2 = '0.48, (P &lt; 0.0001)], while weaker correlations were observed with CD8+ T cells (R 2 = '0.20, P = 0.01), IL-6 (R 2 = +0.16, P = 0.002) and soluble CD14 (R 2 = +0.09, P = 0.05). Patients with higher pre-ART HIV DNA showed lower rate and delayed VIROlogical response (defined as HIV RNA ≤50 copies/mL), compared with those having lower HIV DNA (67.2% for &gt;10 € 000, 81.1% for 1000-10 € 000 and 86.4% for 10-1000 copies/10 6 CD4+ T cells; P = 0.0004). Higher pre-ART HIV DNA was also correlated with increased risk of VIROlogical rebound (defined as HIV RNA &gt;50 copies/mL) by 24 months (17.2% for &gt;10 € 000, 7.4% for 1000-10 € 000 and 4.3% for 10-1000 copies/10 6 CD4+ T cells; P = 0.0048). Adjusted HRs of all VIROlogical rebound definitions confirmed these findings (P ≤ 0.02). Conclusions Pre-ART HIV DNA, along with HIV RNA and CD4+ T cell count, should be considered as a new staging marker to better identify people at lower (or higher) risk of viral rebound following achievement of VIROlogical suppression (≤50 copies/mL).

2018 - Pre-exposure Prophylaxis for HIV Infection in the Older Patient: What can be Recommended? [Articolo su rivista]
Franconi, I; Guaraldi, G
abstract

Over the past 15 years, a significant increase in new HIV/AIDS diagnoses has been observed in the elderly population. This new epidemiological shift has been attributed to a longer sex life, lifestyle and changes in sexual behavior, poor sexual health education, and misconceptions about the absence of sexually transmitted disease in later life. Although many biomedical and behavioral interventions have proven useful to prevent sexually transmitted infections and HIV, pre-exposure prophylaxis (PrEP) has been shown to be the most successful biomedical intervention to prevent HIV in high-risk individuals. This approach is based on delivering a fixed dose of tenofovir disoproxil fumarate (300 mg), alone or combined with emtricitabine (300/200 mg) daily or on demand, before and after sexual intercourse. Despite the consistent number of clinical trials proving the effectiveness and safety of this strategy, no studies have focused specifically on elderly people. These individuals, who may benefit substantially from (PrEP), are at a higher risk of experiencing side effects secondary to tenofovir exposure. This review critically discusses the efficacy and safety of PrEP in people aged over 50 years and translates the knowledge of tenofovir management in patients with HIV into monitoring and stopping rules to be used in this special population. We provide practical recommendations to properly identify PrEP candidates among older adults. Furthermore, we define correct case management before and during PrEP delivery, and we suggest stopping rules and alternative sexually transmitted infection prevention strategies.

2018 - Reliability of serum calcium to phosphorous (Ca/P) ratio as an accurate and inexpensive tool to define disorders of Ca/P metabolism. [Abstract in Atti di Convegno]
Madeo, B.; De Vincentis, S.; Kara, E.; Vescini, F.; Trenti, T.; Guaraldi, G.; Rochira, Vincenzo
abstract

This study investigates the accuracy of a simple, inexpensive index such as the Calcium (Ca) to Phosphorous (P) ratio in the diagnosis of disease of bone metabolism such as hyperparathyroidism and hypoposphoremia.

2018 - Reliabilty of serum Calcium to Phosphorus (Ca/P) ratio as an accurate and inexpensive tool to define disorders of Ca-P metabolism: preliminary data [Abstract in Rivista]
De Vincentis, S.; Monzani, M.; Kara, E.; Guaraldi, G.; Rochira, V.; Madeo, Bruno
abstract

Background: Primary hyperparathyroidism (PHPT) is the third most common endocrine disorder. The Ca/P ratio is an accurate tool to differentiate patients with PHPT (>3.5 if Ca and P are expressed in mg/dl) from healthy subjects [1]. The reliability of this index is based on the fact that serum Ca and P are inversely related together. However, other disorders of the Ca-P metabolism, such as hypophosphoremia (HypoP), might impair the Ca/P ratio. Aim: To validate the accuracy of Ca/P ratio in the diagnosis of Ca-P metabolism disorders, including also patients with documented HypoP. Methods: A single-center, retrospective, case-control study was carried out, including 130 patients with documented PHPT and 300 patients with HypoP, compared with 120 controls. HypoP patients were enrolled among HIV-infected patients on HAART treatment from the large Modena cohort. The main outcome measures were: serum Ca, P, parathyroid hormone (PTH), 25-OH vitamin D, albumin and creatinine. Statistical analysis: Comparisons among groups were performed by the nonparametric Kruskal-Wallis, followed by the Dunn’s post hoc test. The diagnostic accuracy of Ca/P ratio was investigated by receiver operator characteristics (ROC) curves in order to define cut-off points (with the highest sensitivity and specificity). Results: The Ca/P ratio was significantly higher in the group of PHPT together with HypoP, compared to controls (P<0.0001). Also Ca and PTH were significantly different among groups, in particular they were higher (P<0.0001) in PHPT than both controls and HypoP, as expected. At ROC curves analysis, the cut-off of 3.6 for Ca/P ratio was able to identify patients with PHPT and HypoP (sensitivity 91%; specificity 93%). Among patients with Ca/P ratio above 3.6, the thresholds of 10.2 mg/dl for serum Ca (sensitivity 91%; specificity 98%) and of 83.6 pg/ml for PTH (sensitivity 92%; specificity 93%) were defined for the specific diagnosis of PHPT. Conclusions: In this study we confirm the role of serum Ca/P ratio as a reliable index to diagnose a Ca-P metabolism disorder, especially PHPT and HypoP. In clinical practice, when a Ca/P ratio above 3.6 is found, the presence of serum Ca>10.2 mg/dl or PTH>83.6 pg/ml is able to discriminate patients with PHPT from those with HypoP. Reference: 1. Madeo et al, Serum Calcium to Phosphorous (Ca/P) Ratio Is a Simple, Inexpensive and Accurate Tool in the Diagnosis of Primary Hyperparathyroidism. JRBM Plus, 2017. DOI: 10.1002/jbm4.10019.

2018 - Role of tenofovir alafenamide in the jungle of antiretroviral prescription [Articolo su rivista]
Guaraldi, Giovanni
abstract

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2018 - Serum sodium is inversely related to frailty and bone mineral density (BMD) in human immunodeficiency virus (HIV)-infected patients [Abstract in Rivista]
De Vincentis, S.; Decaroli, MARIA CHIARA; Diazzi, C.; Santi, D.; Carli, F.; Zona, S.; Guaraldi, G.; Rochira, V.
abstract

Background HIV-infected patients are predisposed to an increased risk of hyponatremia. In healthy population, low sodium is associated with impaired health status and reduced BMD, but less is known about this association in HIV-infection. Aim To investigate the relationship between serum sodium, frailty and BMD in a large cohort of HIV-infected patients. Methodology A retrospective, observational, cohort study on adult HIV-infected patients (age R18 years), attending the Multidisciplinary Metabolic Clinic of Modena, was carried out including all sodium examinations performed at the Modena lab from 2007 to 2017 available in a large database. Laboratory ranges of normality for sodium (136–146mEq/l) were used to subdivide records in hyponatremic (HypoNa), hypernatremic (HyperNa) and normonatremic (NormoNa) groups. BMD was measured at total body, lumbar spine (L1–L4) and total hip using a Hologic QDR-2000 densitometer (DXA). Frailty was calculated through 38-item multimorbidity frailty index. Statistical analysis Parameters were not normally distributed and Kruskal-Wallis test, followed by Dunn’s test, was used to compare continuous variables. Correlations were performed using linear regression models. Results 8101 records (5454 from males and 2647 from females) of serum sodium (mean 139.4G3.1 mEq/l) evaluated in HIV-infected patients (mean age 49.0G7.9 years) were considered. 617 (7.6%), HypoNa, 44 (0.5%) HyperNa and 7440 (91.8%) NormoNa were found. Frailty score was inversely related to serum sodium (rZK0.174, R2Z0.03, P!0.0001), even after the exclusion of HyperNa group (RZK0.191, R2Z0.036, P!0.0001). Frailty was significantly higher in HypoNa than NormoNa (P!0.001). Considering results at DXA examination, BMD was normal in 30.3% and reduced in 69.7% (54.8% osteopenia, 14.9% osteoporosis). Total body BMD, but not femoral nor lumbar, directly correlated with serum sodium (RZ0.049, P!0.001) and it was significantly lower in HypoNa compared to NormoNa (PZ0.029). Conclusions This study shows that serum sodium is inversely related to frailty, suggesting its potential role as reliable and cheap marker in the HIV-infection follow-up. Furthermore, we demonstrate a direct correlation between sodium and body BMD in HIV-infected patients, similarly to general population. DOI: 10.1530/endoabs.56.P745

2018 - Sofosbuvir plus daclatasvir with or without ribavirin is safe and effective for post-transplant hepatitis C recurrence and severe fibrosis and cirrhosis: A prospective study [Articolo su rivista]
Lionetti, Raffaella; Calvaruso, Vincenza; Piccolo, Paola; Mancusi, Rossella Letizia; Mazzarelli, Chiara; Fagiuoli, Stefano; Montalbano, Marzia; Lenci, Ilaria; Carrai, Paola; Guaraldi, Giovanni; Visco-Comandini, Ubaldo; Milana, Martina; Biolato, Marco; Loiacono, Laura; Valente, Giovanna; Craxì, Antonio; Angelico, Mario; D'offizi, Gianpiero
abstract

In 2012, an Italian Named Patient Program began for hepatitis C virus (HCV)-infected liver transplant (LT) recipients with advanced fibrosis, before approval of direct antiviral agents (DAA), to benefit severely ill patients. The aim of this "real-life" study was to assess treatment efficacy and safety with an extended course of daclatasvir (DCV) plus sofosbuvir (SOF) with or without ribavirin (RBV).

2018 - Switching to dual/monotherapy determines an increase in CD8+ in HIV-infected individuals: An observational cohort study [Articolo su rivista]
Mussini, C.; Lorenzini, P.; Cozzi-Lepri, A.; Marchetti, G.; Rusconi, S.; Gori, A.; Nozza, S.; Lichtner, M.; Antinori, A.; Cossarizza, Andrea; d'Arminio Monforte, A.; Castagna, A.; Castelli, F.; Cauda, R.; Di Perri, G.; Galli, M.; Iardino, R.; Ippolito, G.; Lazzarin, A.; Marchetti, G. C.; Perno, C. F.; Rezza, G.; von Schloesser, F.; Viale, P.; Ceccherini-Silberstein, F.; Girardi, E.; Lo Caputo, S.; Puoti, M.; Andreoni, M.; Ammassari, A.; Balotta, C.; Bandera, A.; Bonfanti, P.; Bonora, S.; Borderi, M.; Calcagno, A.; Calza, L.; Capobianchi, M. R.; Cingolani, A.; Cinque, P.; De Luca, A.; Di Biagio, A.; Gianotti, N.; Guaraldi, G.; Lapadula, G.; Madeddu, G.; Maggiolo, F.; Marcotullio, S.; Monno, L.; Quiros Roldan, E.; Rossotti, R.; Santoro, M. M.; Saracino, A.; Zaccarelli, M.; Fanti, I.; Galli, L.; Rodano, A.; Shanyinde, M.; Tavelli, A.; Carletti, F.; Carrara, S.; Di Caro, A.; Graziano, S.; Petrone, F.; Prota, G.; Quartu, S.; Truffa, S.; Giacometti, A.; Costantini, A.; Barocci, V.; Angarano, G.; Santoro, C.; Suardi, C.; Donati, V.; Verucchi, G.; Minardi, C.; Quirino, T.; Abeli, C.; Manconi, P. E.; Piano, P.; Cacopardo, B.; Celesia, B.; Vecchiet, J.; Falasca, K.; Sighinolfi, L.; Segala, D.; Blanc, P.; Vichi, F.; Cassola, G.; Viscoli, C.; Alessandrini, A.; Bobbio, N.; Mazzarello, G.; Mastroianni, C.; Pozzetto, I.; Caramma, I.; Chiodera, A.; Milini, P.; Rizzardini, G.; Moioli, M. C.; Piolini, R.; Ridolfo, A. L.; Salpietro, S.; Tincati, C.; Puzzolante, C.; Abrescia, N.; Chirianni, A.; Borgia, G.; Orlando, R.; Bonadies, G.; Di Martino, F.; Gentile, I.; Maddaloni, L.; Cattelan, A. M.; Marinello, S.; Cascio, A.; Colomba, C.; Baldelli, F.; Schiaroli, E.; Parruti, G.; Sozio, F.; Magnani, G.; Ursitti, M. A.; Cristaudo, A.; Vullo, V.; Acinapura, R.; Baldin, G.; Capozzi, M.; Cicalini, S.; Fontanelli Sulekova, L.; Iaiani, G.; Latini, A.; Mastrorosa, I.; Plazzi, M. M.; Savinelli, S.; Vergori, A.; Cecchetto, M.; Viviani, F.; Bagella, P.; Rossetti, B.; Franco, A.; Fontana Del Vecchio, R.; Francisci, D.; Di Giuli, C.; Caramello, P.; Orofino, G. C.; Sciandra, M.; Bassetti, M.; Londero, A.; Pellizzer, G.; Manfrin, V.; Starnini, G.; Ialungo, A.
abstract

Background: The CD4/CD8 ratio has been associated with the risk of AIDS and non-AIDS events. We describe trends in immunological parameters in people who underwent a switch to monotherapy or dual therapy, compared to a control group remaining on triple antiretroviral therapy (ART). Methods: We included patients in Icona who started a three-drug combination ART regimen from an ART-naïve status and achieved a viral load ≤ 50 copies/mL; they were subsequently switched to another triple or to a mono or double regimen. Standard linear regression at fixed points in time (12-24 months after the switch) and linear mixed model analysis with random intercepts and slopes were used to compare CD4 and CD8 counts and their ratio over time according to regimen types (triple vs. dual and vs. mono). Results: A total of 1241 patients were included; 1073 switched to triple regimens, 104 to dual (72 with 1 nucleoside reverse transcriptase inhibitor (NRTI), 32 NRTI-sparing), and 64 to monotherapy. At 12 months after the switch, for the multivariable linear regression the mean change in the log10 CD4/CD8 ratio for patients on dual therapy was -0.03 (95% confidence interval (CI) -0.05, -0.0002), and the mean change in CD8 count was +99 (95% CI +12.1, +186.3), taking those on triple therapy as reference. In contrast, there was no evidence for a difference in CD4 count change. When using all counts, there was evidence for a significant difference in the slope of the ratio and CD8 count between people who were switched to triple (points/year change ratio = +0.056, CD8 = -25.7) and those to dual regimen (ratio = -0.029, CD8 = +110.4). Conclusions: We found an increase in CD8 lymphocytes in people who were switched to dual regimens compared to those who were switched to triple. Patients on monotherapy did not show significant differences. The long-term implications of this difference should be ascertained.

2018 - Testosterone (T) and estradiol (E2) are poorly associated to the reduction of bone mineral density (BMD) in Young/Middle Aged Men with Human immunodeficiency virus (HIV). [Abstract in Atti di Convegno]
De Vincentis, S.; Decaroli, M. C.; Diazzi, C.; Morini, Federica; Bertani, D.; Fanelli, F.; Mezzullo, M.; Santi, D.; Pagotto, U.; Guaraldi, G.; Rochira, Vincenzo
abstract

Background: Osteopenia and osteoporosis, as well as hypogonadism, are common findings in men with HIV- infection and they occur at a younger age than healthy subjects. The reduction of BMD is due to both HIV-related and HIV-unrelated factors. Previous studies suggest that T deficiency is not or poorly associated with reduced BMD in HIV context. On the other hand, estrogens are consid- ered more important than androgens for bone health in general population, but data about their role in HIV- infected men are still scanty. Objective: To investigate the relationship between BMD and circulating sex steroids assessed by Liquid Chro- matography tandem Mass Spectrometry (LC-MS/MS) in a cohort of young/middle aged HIV-infected men. Methods: Prospective, cross-sectional, observational study on 233 consecutive HIV-infected male patients with ongo- ing Highly Active Antiretroviral Therapy (HAART), attend- ing the Multidisciplinary Metabolic Clinic of Modena. Body composition and BMD at total body, lumbar spine (L1 to L4) and total hip were measured using a Hologic QDR-2000 densitometer (DXA). LC-MS/MS was used for hormonal assays. Statistical analysis: The nonparametric Mann–Whitney U test was used for group comparisons because variables were not normally distributed at the Kolmogorov-Smirnov test. Correlations were performed using linear regression models. Results: Two hundred and thirty-three HIV-infected patients were enrolled (mean age 45.29 ! 5.33 years) with average duration of HIV-infection of 190.8 ! 102.8 months. Eight patients (3.4%) had hypogonadism, defined as total T serum levels below 300 ng/dL. Considering results at DXA examination, BMD was normal in 36.5% and reduced in 63.5% (55.8% osteopenia, 7.7% osteoporo- sis). Both total T and E2 did not significantly differ com- paring patients with normal BMD to patients with reduced BMD. Body and lumbar BMD did not show any significant difference between eugonadal patients and patients with low T and/or low E2, while both femoral BMD and femoral T-score were significantly higher in patients with E2 above 20 pg/mL than in those with E2 below 20 pg/mL (p = 0.043 and p = 0.033, respectively). At linear and step- wise multiple regression analyses, BMD was positively associated with total lean mass (R2 = 0.154, p < 0.0001); apart from it, neither T nor E2 correlated with BMD and T- score at any site. Conclusion: Classical factors associated to BMD as E2 and T seem to be less relevant in this model of male osteoporo- sis. Other specific HIV-related factors, such as changes in body composition and consequent lipodystrophy, could be more deeply involved than sex steroids as potential mecha- nisms in bone loss in this setting. Finally, we confirm the high prevalence of reduced BMD in young/middle aged HIV-infected men, representing one of the clinical hallmarks of the premature aging process related to HIV infection.

2018 - The ‘COmorBidity in Relation to AIDS’ (COBRA) cohort: Design, methods and participant characteristics [Articolo su rivista]
De Francesco, Davide; Wit, Ferdinand W.; Cole, James H.; Kootstra, Neeltje A.; Winston, Alan; Sabin, Caroline A.; Underwood, Jonathan; Van Zoest, Rosan A.; Schouten, Judith; Kooij, Katherine W.; Prins, Maria; Guaraldi, Giovanni; Caan, Matthan W. A.; Burger, David; Franceschi, Claudio; Libert, Claude; Bürkle, Alexander; Reiss, Peter
abstract

Background Persons living with HIV on combination antiretroviral therapy (cART) may be at increased risk of the development of age-associated non-communicable comorbidities (AANCC) at relatively young age. It has therefore been hypothesised that such individuals, despite effective cART, may be prone to accelerated aging. Objective The COmorBidity in Relation to AIDS (COBRA) cohort study was designed to investigate the potential causal link between HIV and AANCC, amongst others, in a cohort of middle-aged individuals with HIV with sustained viral suppression on cART and otherwise comparable HIV-negative controls. Methods Longitudinal cohort study of HIV-positive subjects 45 years of age, with sustained HIV suppression on cART recruited from two large European HIV treatment centres and similarly-aged HIV-negative controls recruited from sexual health centres and targeted community groups. Both HIV-positive and HIV-negative subjects were assessed at study entry and again at follow-up after 2 years. Results Of the 134 HIV-positive individuals with a median (IQR) age of 56 (51, 62) years recruited, 93% were male, 88% of white ethnicity and 86% were men who have sex with men (MSM). Similarly, the 79 HIV-negative subjects had a median (IQR) age of 57 (52, 64) and 92% were male, 97% of white ethnicity and 80% were MSM. Conclusions The results from the COBRA study will be a significant resource to understand the link between HIV and AANCC and the pathogenic mechanisms underlying this link. COBRA will inform future development of novel prognostic tools for earlier diagnosis of AANCC and of novel interventions which, as an adjunct to cART, may prevent AANCC.

2018 - The increasing burden and complexity of multi-morbidity and polypharmacy in geriatric HIV patients: a cross sectional study of people aged 65 - 74 years and more than 75 years [Articolo su rivista]
Guaraldi, G; Malagoli, A; Calcagno, A; Mussi, C; Celesia, B M; Carli, F; Piconi, S; De Socio, G V; Cattelan, A M; Orofino, G; Riva, A; Focà, E; Nozza, S; Di Perri, G
abstract

Geriatric Patients Living with HIV/AIDS (GEPPO) is a new prospective observational multicentre cohort consisting of all the HIV-positive geriatric patients being treated at 10 clinics in Italy, and HIV-negative controls attending a single geriatric clinic. The aim of this analysis of the GEPPO cohort was to compare prevalence and risk factors of individual non-communicable diseases (NCD), multi-morbidity (MM) and polypharmacy (PP) amongst HIV positive and HIV negative controls at enrolment into the GEPPO cohort.

2018 - The Relationships between Total Body, Lumbar Spine and Femoral Neck Bone Mineral Density T-Scores for Diagnosis of Low Bone Mass in HIVInfected Patients [Articolo su rivista]
Rosenthall, L; Falutz, J; Guaraldi, G
abstract

Background: The total bone mineral density T-score cutoff for low bone mass underestimates the frequency shown by femoral neck and lumbar T-score cutoffs. Objective: To determine whether a total body DXA T-score cutoff can be found that will produce results similar those obtained by local measurements of the femoral neck and lumbar spine. Methodology: Participants were all HIV-infected; 1730 males and 840 females. T-score correlations of the three sites were obtained. ROC analyses were performed to obtain the T-score cutoffs for the total body that would produce results that best matched those of the femoral neck and lumbar spine. Low bone mass was defined as a T-score &lt;-1, which includes both osteopenia and osteoporosis categories as defined by the World Health Organization (WHO). The efficacy of the derived T-score cutoffs were determined by cross tabulation of the modified total body classifications against the femoral neck and lumbar spine classification, and rated by the kappa coefficient of agreement and percent of agreement (concordance). Results: Spearman rank correlations varied from 0.570 to 0.752 between total body, lumbar spine and femoral neck T-scores. Area under the ROC curve varied from 0.777 to 0.874 for the different paired sites. The T-score cutoffs for the total body were selected from the ROC curves at a point where the sum of the sensitivity and specificity is a maximum. Cross tabulation of the binary categories. i.e., normal or abnormal, of the total body using the derived T-score cutoffs against those of the femoral neck and lumbar spine registered a reduction of false negatives, but it was associated with a consistent increase in the number of false positives. The resultant kappa coefficients of agreement varied from 0.429 to 0.564; a moderate rating when perfect agreement is 1.0. Conclusion: The modification of the total body T-score cutoffs for the disclosure of low bone mass at the femoral neck and lumbar spine is not sufficiently accurate for clinical application, in particular fracture risk prediction.

2018 - Treatment rate for HCV in the direct acting antivirals era in HIV co-infected patients: data from an italian cohort [Articolo su rivista]
Cuomo, Gianluca; Puzzolante, Cinzia; Lazzaretti, Claudia; Guaraldi, Giovanni; Borghi, Vanni; Mussini, Cristina
abstract

New Direct Antiviral Agents (DAA) are now effective in HCV infection; persons living with HIV (PLWH) were undertreated. Aim of this study was to describe the management of HCV treatment in a HIV/HCV cohort during a 16 years period.

2017 - A frailty index predicts post-liver transplant morbidity and mortality in HIV-positive patients [Articolo su rivista]
Guaraldi, Giovanni; Dolci, Giovanni; Zona, Stefano; Tarantino, Giuseppe; Serra, Valentina; Ballarin, Roberto; Franceschini, Erica; Codeluppi, Mauro; Brothers, Thomas D.; Mussini, Cristina; DI BENEDETTO, Fabrizio
abstract

Background: We hypothesized that frailty acts as a measure of health outcomes in the context of LT. The aim of this study was to explore frailty index across LT, as a measure of morbidity and mortality. This was a retrospective observational study including all consecutive 47 HIV+patients who received LT in Modena, Italy from 2003 to June 2015. Methods: frailty index (FI) was constructed from 30 health variables. It was used both as a continuous score and as a categorical variable, defining 'most frail' a FI > 0.45. FI change across transplant (deltaFI, ΔFI) was calculated as the difference between year 1 FI (FI-Y1) and pre-transplant FI (FI-t0). The outcomes measures were mortality and "otpimal LT" (defined as being alive without multi-morbidity). Results: Median value of FI-t0 was 0.48 (IQR 0.42-0.52), FI-Y1 was 0.31 (IQR 0.26-0.41). At year five mortality rate was 45%, "optimal transplant" rate at year 1 was 38%. All the patients who died in the post-LT were most frail in the pre-LT. ΔFI was a predictor of mortality after correction for age and MELD (HR = 1.10, p = 0.006) and was inversely associated with optimal transplant after correction for age (HR = 1.04, p = 0.01). Conclusions: We validated FI as a valuable health measure in HIV transplant. In particular, we found a relevant correlation between FI strata at baseline and mortality and a statistically significant correlation between, ΔFI and survival rate.

2017 - Active HCV Replication but Not HCV or CMV Seropositive Status Is Associated With Incident and Prevalent Type 2 Diabetes in Persons Living With HIV [Articolo su rivista]
De Luca, A; Lorenzini, P; Castagna, A; Puoti, M; Gianotti, N; Castelli, F; Mastroianni, C; Maggiolo, F; Antinori, A; Guaraldi, Giovanni; Lichtner, M; Monforte, Ad
abstract

Objective: To analyze the association between chronic hepatitis C virus (HCV) and cytomegalovirus (CMV) infections with type 2 diabetes in HIV-infected patients.Methods: HIV-1-infected patients enrolled in ICONA, a prospective cohort study involving 42 tertiary care centers in Italy, were selected with the following characteristics: for the diabetes incidence analysis, all patients with available CMV IgG results (first available test = baseline) and without type 2 diabetes were followed until onset of type 2 diabetes, last available clinical follow-up, death or September 30, 2014, whichever occurred first; for the prevalence analysis, all ICONA patients were analyzed at their last follow-up visit. Main outcome measures were the new onset of type 2 diabetes (incidence analysis) and the prevalence of type 2 diabetes at last follow-up.Results: During 38,062 person-years of follow-up (PYFU) in 6505 individuals, we observed 140 cases of incident type 2 diabetes (Incidence rate 3.7, 95% CI: 3.1 to 4.3, per 1000 PYFU). In a multivariable Poisson regression model, HCV-antibody (Ab) +/HCV RNA+ patients [adjusted relative rate versus HCV-Ab negative 1.73 (95% CI: 1.08 to 2.78)] but not HCV Ab+RNA- or CMV IgG+ patients, had a higher risk of diabetes. Among 12,001 patients, 306 (2.5%) prevalent cases of type 2 diabetes were detected. HCV Ab+RNA+ status was independently associated with prevalent diabetes (adjusted Odds Ratio vs HCV Ab- 2.49; 95% CI: 1.08 to 5.74), whereas HCV-Ab+/HCV RNA- and CMV IgG+ status were not.Conclusion: In HIV-infected individuals, active HCV replication but not prior HCV exposure or latent CMV infection is associated with incident and prevalent type 2 diabetes.

2017 - Ageing and inflammation in patients with HIV infection [Articolo su rivista]
Nasi, Milena; DE BIASI, Sara; Gibellini, Lara; Bianchini, Elena; Pecorini, S.; Bacca, V.; Guaraldi, Giovanni; Mussini, Cristina; Pinti, Marcello; Cossarizza, Andrea
abstract

Nowadays, HIV+ patients have an expected lifespan that is only slightly shorter than healthy individuals. For this reason, along with the fact that infection can be acquired at a relatively advanced age, the effects of ageing on HIV+ people have begun to be evident. Successful anti-viral treatment is, on one hand, responsible for the development of side effects related to drug toxicity; on the other hand, it is not able to inhibit the onset of several complications caused by persistent immune activation and chronic inflammation. Therefore, patients with a relatively advanced age, i.e. aged more than 50 years, can experience pathologies that affect much older citizens. HIV+ individuals with non-AIDS-related complications can thus come to the attention of clinicians because of the presence of neurocognitive disorders, cardiovascular diseases, metabolic syndrome, bone abnormalities and non-HIV-associated cancers. Chronic inflammation and immune activation, observed typically in elderly people and defined as 'inflammaging', can be present in HIV+ patients who experience a type of premature ageing, which affects the quality of life significantly. This relatively new condition is extremely complex, and important factors have been identified as well as the traditional behavioural risk factors, e.g. the toxicity of anti-retroviral treatments and the above-mentioned chronic inflammation leading to a functional decline and a vulnerability to injury or pathologies. Here, we discuss the role of inflammation and immune activation on the most important non-AIDS-related complications of chronic HIV infection, and the contribution of aging per se to this scenario.

2017 - Aging in HIV-Infected Subjects: A New Scenario and a New View [Articolo su rivista]
Negredo, Eugenia; Back, David; Blanco, José-Ramón; Blanco, Julià; Erlandson, Kristine M; Garolera, Maite; Guaraldi, Giovanni; Mallon, Patrick; Moltó, José; Serra, José Antonio; Clotet, Bonaventura
abstract

The prevalence of HIV-infected people aged 50 years or older is increasing rapidly; the proportion will increase from 28% to 73% in 2030. In addition, HIV-infected individuals may be more vulnerable to age-related condition. There is growing evidence that the prevalence of comorbidities and other age-related conditions (geriatric syndromes, functional or neurocognitive/mental problems, polypharmacy, and social difficulties) is higher in the HIV-infected population than in their uninfected counterparts. However, despite the potential impact of this situation on health care, little information exists about the optimal clinical management of older HIV-infected people. Here we examine the age-related conditions in older HIV-infected persons and address clinical management according to author expertise and published literature. Our aim is to advance the debate about the most appropriate management of this population, including less well-studied aspects, such as frequency of screening for psychological/mental and social and functional capabilities.

2017 - Amniocentesis and chorionic villus sampling in HIV-infected pregnant women: a multicentre case series [Articolo su rivista]
Floridia, M.; Masuelli, G.; Meloni, A.; Cetin, I.; Tamburrini, E.; Cavaliere, A. F.; Dalzero, S.; Sansone, M.; Alberico, S.; Guerra, B.; Spinillo, A.; Chiado Fiorio Tin, M.; Ravizza, M.; Mori, F.; Ortolani, P.; dalle Nogare, E. R.; Di Lorenzo, F.; Sterrantino, G.; Meli, M.; Polemi, S.; Nocentini, J.; Baldini, M.; Montorzi, G.; Mazzetti, M.; Rogasi, P.; Borchi, B.; Vichi, F.; Del Pin, B.; Pinter, E.; Anzalone, E.; Marocco, R.; Mastroianni, C.; Mercurio, V. S.; Carocci, A.; Grilli, E.; Maccabruni, A.; Zaramella, M.; Mariani, B.; Natalini Raponi, G.; Guaraldi, G.; Nardini, G.; Stentarelli, C.; Beghetto, B.; Degli Antoni, A. M.; Molinari, A.; Crisalli, M. P.; Donisi, A.; Piepoli, M.; Cerri, V.; Zuccotti, G.; Giacomet, V.; Coletto, S.; Di Nello, F.; Madia, C.; Placido, G.; Vivarelli, A.; Castelli, P.; Savalli, F.; Portelli, V.; Sabbatini, F.; Francisci, D.; Bernini, L.; Grossi, P.; Rizzi, L.; Maso, G.; Airoud, M.; Soppelsa, G.; Dedoni, M.; Cuboni, C.; Ortu, F.; Piano, P.; Citernesi, A.; Bordoni Vicini, I.; Luzi, K.; Roccio, M.; Vimercati, A.; Miccolis, A.; De Gennaro, A.; Cervi, F.; Simonazzi, G.; Margarito, E.; Capretti, M. G.; Marsico, C.; Faldella, G.; Martinelli, P.; Agangi, A.; Capone, A.; Maruotti, G. M.; Tibaldi, C.; Trentini, L.; Todros, T.; Frisina, V.; Brambilla, T.; Savasi, V.; Personeni, C.; Giaquinto, C.; Fiscon, M.; Rubino, E.; Bucceri, A.; Matrone, R.; Scaravelli, G.; Genovese, O.; Cafforio, C.; Pinnetti, C.; Liuzzi, G.; Tozzi, V.; Massetti, P.; Casadei, A. M.; Cellini, M.; Castelli Gattinara, G.; Marconi, A. M.; Sacchi, V.; Ierardi, M.; Polizzi, C.; Mattei, A.; Pirillo, M. F.; Amici, R.; Galluzzo, C. M.; Donnini, S.; Baroncelli, S.; Villani, P.; Cusato, M.; Cerioli, A.; De Martino, M.; Mastroiacovo, P.; Parazzini, F.; Vella, S.
abstract

Objectives: To assess in pregnant women with HIV the rates of amniocentesis and chorionic villus sampling (CVS), and the outcomes associated with such procedures. Design: Observational study. Data from the Italian National Program on Surveillance on Antiretroviral Treatment in Pregnancy were used. Setting: University and hospital clinics. Population: Pregnant women with HIV. Methods: Temporal trends were analysed by analysis of variance and by the Chi-square test for trend. Quantitative variables were compared by Student's t-test and categorical data by the Chi-square test, with odds ratios and 95% confidence intervals calculated. Main outcome measures: Rate of invasive testing, intrauterine death, HIV transmission. Results: Between 2001 and 2015, among 2065 pregnancies in women with HIV, 113 (5.5%) had invasive tests performed. The procedures were conducted under antiretroviral treatment in 99 cases (87.6%), with a significant increase over time in the proportion of tests performed under highly active antiretroviral therapy (HAART) (100% in 2011–2015). Three intrauterine deaths were observed (2.6%), and 14 pregnancies were terminated because of fetal anomalies. Among 96 live newborns, eight had no information available on HIV status. Among the remaining 88 cases with either amniocentesis (n = 75), CVS (n = 12), or both (n = 1), two HIV transmissions occurred (2.3%). No HIV transmission occurred among the women who were on HAART at the time of invasive testing, and none after 2005. Conclusions: The findings reinforce the assumption that invasive prenatal testing does not increase the risk of HIV vertical transmission among pregnant women under suppressive antiretroviral treatment. Tweetable abstract: No HIV transmission occurred among women who underwent amniocentesis or CVS under effective anti-HIV regimens.

2017 - Antiretroviral therapies and cardiovascular risk: True or false? [Articolo su rivista]
Guaraldi, Giovanni; Raggi, Paolo
abstract

not available

2017 - Antiretroviral therapy in geriatric HIV patients: the GEPPO cohort study [Articolo su rivista]
Nozza, Silvia; Malagoli, Andrea; Maia, Lilian; Calcagno, Andrea; Focà, Emanuele; De Socio, Giuseppe; Piconi, Stefania; Orofino, Giancarlo; Cattelan, Anna Maria; Celesia, Benedetto Maurizio; Gervasi, Elena; Guaraldi, Giovanni
abstract

GEPPO is a prospective observational multi-centric cohort including HIV-infected geriatric patients. We hypothesized that the GEPPO cohort may help characterize antiretroviral (ARV) prescribing criteria used in real life by Italian infectious disease (ID) physicians.

2017 - Atherosclerosis in frailty: Not frailty in atherosclerosis [Articolo su rivista]
Guaraldi, Giovanni; Raggi, Paolo
abstract

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2017 - Cardiovascular Risk Prediction in Patients With Human Immunodeficiency Virus [Articolo su rivista]
Raggi, Paolo; De Francesco, Davide; Guaraldi, Giovanni
abstract

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2017 - Clinical implications of aging with HIV infection: perspectives and the future medical care agenda [Articolo su rivista]
Guaraldi, Giovanni; Palella, Frank J.
abstract

The increasing number of aging HIV-infected (HIV+) persons comprises a unique population at risk for illnesses and syndromes traditionally associated with the elderly. As a result, similar to the current need for primary care providers to manage chronic noninfectious comorbidities among aging persons with well controlled HIV infection, HIV clinical care will need to routinely involve geriatric medicine in a new HIV-geriatric discipline. The objective of this article is to provide a conceptual framework in which HIV and geriatric management considerations for healthcare professionals caring for HIV+ persons are integrated. The provision of contemporary HIV clinical care extends well beyond the achievement of HIV virologic suppression and antiretroviral therapy management and includes a need for careful characterization of geriatric syndromes based upon functional capacity and extent of disability. Screening for geriatric syndromes is both a multidisciplinary and multidimensional process, designed to evaluate an older person's functional ability, physical health, cognition, overall mental health, and socio-environmental circumstances. Although routine incorporation of geriatric assessment into clinical trials involving HIV+ persons is feasible, a current challenge is the availability of a consensus clinical definition of frailty or vulnerability. To maximize the efficiency, value, and convenience of outpatient care visits for older HIV+ persons, these visits should include encounters with multiple providers, including primary care clinicians, social workers, and geriatricians. Challenges may exist in the routine provision of these assessments to older HIV+ persons, but clearly such cross-disciplinary collaboration will not only markedly enhance the care of aging HIV+ persons but may also constitute a model of successful healthcare management that can be applied to all aging persons with changing healthcare needs.

2017 - Clinical Utility of Epstein-Barr Virus Viral Load Monitoring and Risk Factors for Posttransplant Lymphoproliferative Disorders After Kidney Transplantation [Articolo su rivista]
Franceschini, Erica; Plessi, Jessica; Zona, Stefano; Santoro, Antonella; Digaetano, Margherita; Fontana, Francesco; Alfano, Gaetano; Guaraldi, Giovanni; Comoli, Patrizia; Facchini, Francesca; Potenza, Leonardo; Gennari, William; Codeluppi, Mauro; Luppi, Mario; Cappelli, Gianni; Gyssens, Inge C.; Mussini, Cristina
abstract

Background. Posttransplant lymphoproliferative disease (PTLD) is an important cause of morbidity and mortality in solid organ transplants. Epstein Barr virus (EBV) plays a major role in PTLD development. Guidelines recommend EBV viral load (VL) monitoring in high-risk populations in the first year. Methods. Retrospective observational study in all adult patients who had at least 1 EBV-VL performed in the postkidney transplant (KT) period from January 2005 to December 2014 at the Policlinico Modena Hospital. We compared patients with negative EBV-DNA to patients with positive EBV-DNA and we described PTLD developed in the study period. Results.One hundred ninety (36.3%) KT patients of 523 were screened for EBV-DNA with 796 samples. One hundred twenty-eight (67.4%) of 190 tested patients presented at least 1 positive sample for EBV. Older age, the use of sirolimus, everolimus, and steroids were associated with EBV-DNA positivity in the univariate analysis. Nine (1.7%) of 523 patients had PTLD. Incidence rate of PTLD in the KT cohort was 0.19/100 person year follow-up (95% confidence interval, 0.09-0.37). One of 9 patients developed early PTLD and was a high-risk patient. Only this PTLD case was positive for EBV. No PTLD case had an EBV-VL superior to 4000 copies/mL. Conclusions. Our results suggest that the keystone of PTLD diagnosis is the clinical suspicion. Our study suggests that, in line with guidelines, EBV-VL assays may be avoided in low-risk patients in the absence of a strong clinical PTLD suspicion without increasing patients' risk of developing PTLD. This represents a safe and cost-saving clinical strategy for our center

2017 - Correlates of frailty phenotype and frailty index and their associations with clinical outcomes [Articolo su rivista]
Guaraldi, Giovanni; Malagoli, Andrea; Theou, O; Brothers, T. D; Wallace, Lmk; Torelli, Riccardo; Mussini, Cristina; Sartini, Silvana; Kirkland, S. A; Rockwood, K.
abstract

Frailty is a predictor of adverse health outcomes and can be measured across the life course, including among people living with HIV. The purpose of this study was to examine two commonly used measures of frailty - the frailty index (FI) and frailty phenotype - to assess common characteristics and to describe associations with multimorbidity, falls, and disability in people aging with HIV.

2017 - Efficacy and tolerability of switching to a dual therapy with darunavir/ritonavir plus raltegravir in HIV-infected patients with HIV-1 RNA ≤50 cp/mL [Articolo su rivista]
Madeddu, G.; Rusconi, S.; Cozzi-Lepri, A.; Di Giambenedetto, S.; Bonora, S.; Carbone, A.; De Luca, A.; Gianotti, N.; Di Biagio, A.; Antinori, A.; d'Arminio Monforte, A.; Andreoni, M.; Angarano, G.; Castelli, F.; Cauda, R.; Di Perri, G.; Galli, M.; Iardino, R.; Ippolito, G.; Lazzarin, A.; Perno, C. F.; von Schloesser, F.; Viale, P.; Castagna, A.; Ceccherini-Silberstein, F.; Girardi, E.; Lo Caputo, S.; Mussini, C.; Puoti, M.; Ammassari, A.; Balotta, C.; Bandera, A.; Bonfanti, P.; Borderi, M.; Calcagno, A.; Calza, L.; Capobianchi, M. R.; Cingolani, A.; Cinque, P.; Lichtner, A.; Maggiolo, F.; Marchetti, G.; Marcotullio, S.; Monno, L.; Nozza, S.; Quiros Roldan, E.; Rossotti, R.; Santoro, M. M.; Saracino, A.; Zaccarelli, M.; Fanti, I.; Galli, L.; Lorenzini, P.; Rodano, A.; Shanyinde, M.; Tavelli, A.; Carletti, F.; Carrara, S.; Di Caro, A.; Graziano, S.; Petrone, F.; Prota, G.; Quartu, S.; Truffa, S.; Giacometti, A.; Costantini, A.; Valeriani, C.; Santoro, C.; Suardi, C.; Donati, V.; Verucchi, G.; Minardi, C.; Quirino, T.; Abeli, C.; Manconi, P. E.; Piano, P.; Cacopardo, B.; Celesia, B.; Vecchiet, J.; Falasca, K.; Sighinolfi, L.; Segala, D.; Mazzotta, F.; Vichi, F.; Cassola, G.; Viscoli, C.; Alessandrini, A.; Bobbio, N.; Mazzarello, G.; Mastroianni, C.; Belvisi, V.; Caramma, I.; Chiodera, A.; Castelli, A. P.; Rizzardini, G.; Ridolfo, A. L.; Piolini, R.; Salpietro, S.; Carenzi, L.; Moioli, M. C.; Puzzolante, C.; Gori, A.; Guaraldi, G.; Lapadula, G.; Abrescia, N.; Chirianni, A.; Borgia, G.; Di Martino, F.; Maddaloni, L.; Gentile, I.; Orlando, R.; Cascio, A.; Colomba, C.; Baldelli, F.; Francisci, D.; Parruti, G.; Ursini, T.; Magnani, G.; Ursitti, M. A.; Vullo, V.; Cristaudo, A.; Baldin, G.; Cicalini, S.; Gallo, L.; Nicastri, E.; Acinapura, R.; Capozzi, M.; Libertone, R.; Savinelli, S.; Latini, A.; Iaiani, G.; Cecchetto, M.; Viviani, F.; Mura, M. S.; Rossetti, B.; Caramello, P.; Orofino, G. C.; Sciandra, M.; Bassetti, M.; Londero, A.; Pellizzer, G.; Manfrin, V.
abstract

Background: Nucleos(t)ide reverse transcriptase inhibitors (NRTI) toxicity may represent a threat for long-term success of combined antiretroviral therapy. Some studies have suggested a possible improvement of NRTI-related toxicity after switching to NRTI-sparing regimens. Objectives: We aimed to explore the efficacy and tolerability of switching to darunavir/ritonavir (DRV/r) plus raltegravir (RAL) while having a viral load (VL) ≤50 copies/mL in the clinical setting. Study design: Treatment-experienced HIV 1-infected patients enrolled in the ICONA Foundation Study cohort were included if they switched their current regimen to DRV/r&nbsp;+&nbsp;RAL with a HIV-RNA ≤50&nbsp;copies/mL. Different definitions of virological failure (VF) and treatment failure (TF) were employed. Kaplan–Meier curves and Cox regression models were performed to estimate time to event probability. Results: We included 72 HIV-infected patients, 22 (31%) of these were female, 31 (43%) men who have sex with men (MSM) amd 15 (21%) had hepatitis co-infections. Median age was 44 (IQR: 35-50) years amd CD4 count was 389 (IQR 283-606) cells/mmc. Median follow-up time for TF was 24 (IQR 9–31)&nbsp;months. Twenty-five discontinuations occurred (60% simplifications); only 2 (8%) were toxicity-driven (lipid elevations). The probability of VF (confirmed VL &gt;50 copies/mL) was estimated at 7% [95% confidence interval (CI) 1–13%] by 12 and 9% (95% CI 2–16%) by 24&nbsp;months. When considering TF, we found a probability of stop/intensification/single VL&nbsp;&gt;&nbsp;200 copies/mL of 13% (95% CI 1–17%) and 22% (95% CI 11–33%) by 12 and 24&nbsp;months. Female gender (adjusted relative hazard, ARH&nbsp;=&nbsp;0.10; 95% CI 0.01–0.74; p&nbsp;=&nbsp;0.024) and older age (AHR&nbsp;=&nbsp;0.50 per 10&nbsp;years older; 95% CI 0.25–0.99; p&nbsp;=&nbsp;0.045) were associated with a lower risk of TF. A previous PI failure was strongly associated with TF (AHR&nbsp;=&nbsp;52.6, 95% CI 3.6–779; p&nbsp;=&nbsp;0.004). Conclusions: DRV/r&nbsp;+&nbsp;RAL is a valuable NRTI-sparing option, especially in female and older patients, with a relatively low risk of VF and good tolerability after 2&nbsp;years since start in an ART-experienced population. However, previous PI-failure should be a limiting factor for this strategy.

2017 - Erratum: Antiretroviral therapy in geriatric HIV patients: The GEPPO cohort study [J Antimicrob Chemother, 72, (2017) (2879-2886)] DOI: 10.1093/jac/dkx169 [Articolo su rivista]
Nozza, S.; Malagoli, A.; Maia, L.; Calcagno, A.; Foca, E.; De Socio, G.; Piconi, S.; Orofino, G.; Cattelan, A. M.; Celesia, B. M.; Gervasi, E.; Guaraldi, G.
abstract

In the original published version of this article the Funding statement was incorrect. The correct statement is: The GEPPO cohort has been designed in the 'Ageing &amp; Frailty Working Group' sponsored by ViiV Healthcare Italy. This error has nowbeen corrected.

2017 - Evolving treatment implementation among HIV- infected pregnant women and their partners: Results from a national surveillance study in Italy, 2001-2015 [Articolo su rivista]
Floridia, M.; Frisina, V.; Ravizza, M.; Marconi, A. M.; Pinnetti, C.; Cetin, I.; Sansone, M.; Molinari, A.; Cervi, F.; Meloni, A.; Luzi, K.; Masuelli, G.; Tamburrini, E.; Ensoli, B.; Moroni, M.; Lazzarin, A.; Sagnelli, E.; Antinori, A.; Carosi, G.; Marcotullio, S.; Mazzotta, F.; Vella, S.; Ammassari, A.; Antonucci, G.; Andreoni, M.; Angarano, G.; Armignacco, O.; Babudieri, S.; Baldelli, F.; Bini, T.; Bonfanti, P.; Bonora, S.; Borderi, M.; Bruno, R.; Bucciardini, R.; Castagna, A.; Cattelan, A. M.; Cauda, R.; Cerioli, A.; Chirianni, A.; Cingolani, A.; Cinque, P.; d'Arminio Monforte, A.; De Carli, G.; De Luca, A.; Di Perri, G.; Di Pietro, M.; El Hamad, I.; Errico, M.; Ferrazzi, E.; Gabrielli, E.; Galli, M.; Giaquinto, C.; Girardi, E.; Gori, A.; Grossi, P.; Guaraldi, G.; Liuzzi, G.; Lo Caputo, S.; Maggiolo, F.; Malena, M.; Maserati, R.; Mastroianni, C.; Matteelli, A.; Morrone, A.; Murri, R.; Mussini, C.; Nasta, P.; Oldrini, M.; Oleari, F.; Orlando, G.; Palu, G.; Pempinello, R.; Perno, C. -F.; Prestileo, T.; Pompa, M. G.; Puoti, M.; Puro, V.; Rancilio, L.; Rasi, G.; Rizzardini, G.; Savasi, V. M.; Signorini, L.; Sighinolfi, L.; Stagnitta, M.; Starace, F.; Starnini, G.; Sterrantino, G.; Suter, F.; Tambussi, G.; Tavio, M.; Torti, C.; Tozzi, V.; Trotta, M. P.; Vaccher, E.; Vigano, A.; Visintini, R.; Vullo, V.; Zuccotti, G. V.; Dell'Isola, S.; Manfredini, V.; Parisi, S.; Pezzoli, M. C.; Zona, S.
abstract

Background The current global and national indications for antiretroviral treatment (ART, usually triple combination therapy) in adolescent and adults, including pregnant women, recommend early ART before immunologic decline, pre-exposure chemoprophylaxis (PrEP), and treatment of HIV-negative partners in serodiscordant couples. There is limited information on the implementation of these recommendations among pregnant women with HIV and their partners. Methods The present analysis was performed in 2016, using data from clinical records of pregnant women with HIV, followed between 2001 and 2015 at hospital or university clinics within a large, nationally representative Italian cohort study. The study period was divided in three intervals of five years each (2001-2005, 2006-2010, 2011-2015), and the analysis evaluated temporal trends in rates of HIV diagnosis in pregnancy, maternal antiretroviral treatment at conception, prevalence of HIV infection among partners of pregnant women with HIV, and proportion of seronegative and seropositive male partners receiving antiretroviral treatment. Results The analysis included 2755 pregnancies in women with HIV. During the three time intervals considered the rate of HIV diagnosis in pregnancy (overall 23.3%), and the distribution of HIV status among male partners (overall 48.7% HIV- negative, 28.6% HIV-positive and 22.8% unknown) remained substantially unchanged. Significant increases were observed in the proportion of women with HIV diagnosed before pregnancy who were on antiretroviral treatment at conception (from 62.0% in 2001-2005 to 81.3% in 2011-2015, P &lt; 0.001), and in the proportion of HIV-positive partners on antiretroviral treatment (from 73.3% in 2001-2005 to 95.8% in 2011-2015, P = 0.002). Antiretroviral treatment was administered in 99.1% of the pregnancies that did not end early because of miscarriage, termination, or intrauterine death, and in 75.3% of those not ending in a live birth. No implementation of antiretroviral treatment was introduced among male HIV-negative partners. Conclusions The results suggest good implementation of antiretroviral treatment among HIV-positive women and their HIV-positive partners, but no implementation, even in recent years, of Pre-Exposure Prophylaxis (PrEP) among uninfected male partners. Further studies should assess the determinants of this occurrence and clarify the attitudes and the potential barriers to PrEP use.

2017 - Geriatric syndromes: How to treat [Articolo su rivista]
Cesari, Matteo; Marzetti, Emanuele; Canevelli, Marco; Guaraldi, Giovanni
abstract

The survival of HIV-infected persons has been increasing over the last years, thanks to the implementation of more effective pharmacological and non-pharmacological interventions. Nevertheless, HIV-infected persons are often “biologically” older than their “chronological” age due to multiple clinical, social, and behavioral conditions of risk. The detection in this population of specific biological features and syndromic conditions typical of advanced age has made the HIV infection an interesting research model of accelerated and accentuated aging. Given such commonalities, it is possible that “biologically aged” HIV-positive persons might benefit from models of adapted and integrated care developed over the years by geriatricians for the management of their frail and complex patients. In this article, possible strategies to face the increasingly prevalent geriatric syndromes in HIV-infected persons are discussed. In particular, it is explained the importance of shifting from the traditional disease-oriented approach into models of care facilitating a multidisciplinary management of frailty.

2017 - Geriatric-HIV medicine: A science in its infancy [Articolo su rivista]
Guaraldi, Giovanni; Cossarizza, Andrea
abstract

not available

2017 - Geriatric-HIV medicine is born [Articolo su rivista]
Guaraldi, Giovanni; Rockwood, Kenneth
abstract

not available

2017 - Growth hormone deficiency and human immunodeficiency virus [Articolo su rivista]
Rochira, Vincenzo; Guaraldi, Giovanni
abstract

Treatment with highly active antiretroviral drugs (HAART) is associated with several endocrine and metabolic comorbidities. Pituitary growth hormone (GH) secretion seems to be altered in human immunodeficiency virus (HIV) infection, and about one-third of patients have biochemical GH deficiency (GHD). We undertake a historical review of the functioning of the GH/insulin-like growth factor-1 (IGF-1) axis in patients with acquired immunodeficiency syndrome, and provide an overview of the main changes of the GH/IGF-1 axis occurring today in patients with HIV. Both spontaneous GH secretion and GH response to provocative stimuli are reduced in patients with HIV infection, especially in those with HIV-related lipodystrophy. The role of fat accumulation on flattened GH secretion is discussed, together with all factors able to potentially interfere with the pituitary secretion of GH. Several factors contribute to the development of GHD, but the pathophysiologic mechanisms involved in the genesis of GHD are complex and not yet fully elucidated owing to the difficulty in separating the effects of HIV infection from those of HAART, comorbidities and body changes. An update on the putative mechanisms involved in the pathogenesis of altered GH secretion in these patients is provided, together with an overview on the therapeutic strategies targeting the GH/IGF-1 axis to counteract fat redistribution associated with HIV-related lipodystrophy. The clinical significance of GHD in the context of HIV infection is discussed. The administration of tesamorelin, a GH releasing hormone analogue, is effective in reducing visceral fat in HIV-infected patients with lipodystrophy. This treatment is promising and safer than treatment with high doses of recombinant human growth hormone, which has several side-effects.

2017 - HBV coinfection is associated with reduced CD4 response to antiretroviral treatment in pregnancy [Articolo su rivista]
Floridia, Marco; Masuelli, Giulia; Tamburrini, Enrica; Spinillo, Arsenio; Simonazzi, Giuliana; Guaraldi, Giovanni; Degli Antoni, Anna Maria; Martinelli, Pasquale; Portelli, Vincenzo; Dalzero, Serena; Ravizza, Marina
abstract

To evaluate the impact of Hepatitis B virus (HBV) coinfection on response to antiretroviral treatment in pregnant women with HIV.

2017 - High cellular monocyte activation in people living with human immunodeficiency virus on combination antiretroviral therapy and lifestyle-matched controls is associated with greater inflammation in cerebrospinal fluid [Articolo su rivista]
Booiman, T.; Wit, F. W.; Maurer, I.; De Francesco, D.; Sabin, C. A.; Harskamp, A. M.; Prins, M.; Garagnani, P.; Pirazzini, C.; Franceschi, C.; Fuchs, D.; Gisslen, M.; Winston, A.; Reiss, P.; Kootstra, N. A.; Schouten, J.; Kooij, K. W.; van Zoest, R. A.; Elsenga, B. C.; Janssen, F. R.; Heidenrijk, M.; Zikkenheiner, W.; van der Valk, M.; Kootstra, N. A.; Harskamp-Holwerda, A. M.; Boeser-Nunnink, B.; Mangas Ruiz, M. M.; Girigorie, A. F.; Villaudy, J.; Frankin, E.; Pasternak, A.; Berkhout, B.; van der Kuyl, T.; Portegies, P.; Schmand, B. A.; Geurtsen, G. J.; ter Stege, J. A.; Klein Twennaar, M.; Majoie, C. B. L. M.; Caan, M. W. A.; Su, T.; Weijer, K.; Bisschop, P. H. L. T.; Kalsbeek, A.; Wezel, M.; Visser, I.; Ruhe, H. G.; Capri, M.; Dall'Olio, F.; Chiricolo, M.; Salvioli, S.; Hoeijmakers, J.; Pothof, J.; Martens, M.; Moll, S.; Berkel, J.; Totte, M.; Kovalev, S.; Zetterberg, H.; Underwood, J.; McDonald, L.; Stott, M.; Legg, K.; Lovell, A.; Erlwein, O.; Doyle, N.; Kingsley, C.; Sharp, D. J.; Leech, R.; Cole, J. H.; Zaheri, S.; Hillebregt, M. M. J.; Ruijs, Y. M. C.; Benschop, D. P.; Burger, D.; de Graaff-Teulen, M.; Guaraldi, G.; Burkle, A.; Sindlinger, T.; Moreno-Villanueva, M.; Keller, A.; de Francesco, D.; Libert, C.; Dewaele, S.
abstract

Background. Increased monocyte activation and intestinal damage have been shown to be predictive for the increased morbidity and mortality observed in treated people living with human immunodeficiency virus (PLHIV). Methods. A cross-sectional analysis of cellular and soluble markers of monocyte activation, coagulation, intestinal damage, and inflammation in plasma and cerebrospinal fluid (CSF) of PLHIV with suppressed plasma viremia on combination antiretroviral therapy and age and demographically comparable HIV-negative individuals participating in the Comorbidity in Relation to AIDS (COBRA) cohort and, where appropriate, age-matched blood bank donors (BBD). Results. People living with HIV, HIV-negative individuals, and BBD had comparable percentages of classical, intermediate, and nonclassical monocytes. Expression of CD163, CD32, CD64, HLA-DR, CD38, CD40, CD86, CD91, CD11c, and CX3CR1 on monocytes did not differ between PLHIV and HIV-negative individuals, but it differed significantly from BBD. Principal component analysis revealed that 57.5% of PLHIV and 62.5% of HIV-negative individuals had a high monocyte activation profile compared with 2.9% of BBD. Cellular monocyte activation in the COBRA cohort was strongly associated with soluble markers of monocyte activation and inflammation in the CSF. Conclusions. People living with HIV and HIV-negative COBRA participants had high levels of cellular monocyte activation compared with age-matched BBD. High monocyte activation was predictive for inflammation in the CSF.

2017 - HIV-DNA content in different CD4+ T-cell subsets correlates with CD4+ cell : CD8+ cell ratio or length of efficient treatment [Articolo su rivista]
Gibellini, Lara; Pecorini, Simone; DE BIASI, Sara; Bianchini, Elena; Digaetano, Margherita; Pinti, Marcello; Carnevale, Gianluca; Borghi, Vanni; Guaraldi, Giovanni; Mussini, Cristina; Cossarizza, Andrea; Nasi, Milena
abstract

Objectives: HIV establishes a latent infection at different degrees within naïve (TN) or central (TCM) and effector memory (TEM) CD4+ T cell. Studying patients in whom HIV production was suppressed by combined antiretroviral therapy, our main aim was to find which factors are related or can influence intracellular viral reservoir in different CD4+ T-cell subsets. Methods: We enrolled 32 HIV+ patients successfully treated for more than 2 years, with a CD4+ T-cell count more than 500 cells/μl and plasma viremia undetectable from at least 1 year. Proviral HIV-DNA, the amount of cells expressing signal-joint T-cell receptor rearrangement excision circles and telomere length were quantified by droplet digital PCR in highly purified, sorted CD4+ T-cell subsets; plasma IL-7 and IL-15 were measured by ELISA. Results: HIV-DNA was significantly lower in TN cells compared with TCM or to TEM. Conversely, TN cells contained more signal-joint T-cell receptor rearrangement excision circles compared with TCM or to TEM; no appreciable changes were observed in telomere length. HIV-DNA content was significantly higher in TN and TCM cells, but not in TEM, from patients with shorter time of treatment, or in those with lower CD4+ : CD8+ ratio. Conclusion: Length of treatment or recovery of CD4+ : CD8+ ratio significantly influences viral reservoir in both TN and TCM. Measuring HIV-DNA in purified lymphocyte populations allows a better monitoring of HIV reservoir and could be useful for designing future eradication strategies.

2017 - Impact of polypharmacy on antiretroviral prescription in people living with HIV. [Articolo su rivista]
Guaraldi, Giovanni; Menozzi, Marianna; Zona, Stefano; Calcagno, Andrea; Domingues Da Silva, Ana Rita; Santoro, Antonella; Malagoli, Andrea; Dolci, Giovanni; Mussi, Chiara; Mussini, Cristina; Cesari, Matteo; Khoo Saye, H.
abstract

OBJECTIVES: To evaluate the relationship between polypharmacy and ART, delivered as conventional multi-tablet three-drug regimens, single-tablet regimens or less-drug regimens (simplified mono or dual regimens). METHODS: We conducted a cross-sectional analysis of electronic data from the prospective Modena HIV Metabolic Clinic Cohort Study. We included the last clinical observation for each patient from January 2006 to December 2015. Polypharmacy was defined as the use of five or more medications (excluding ART). Multi-morbidity was classified as the presence of two or more non-infectious comorbidities. Factors associated with different ART regimens were analysed using multivariable multinomial logistic regression analyses with multi-tablet three-drug regimens as the reference. RESULTS: A total of 2944 patients (33.7% females) were included in the analysis. Multinomial logistic regression analysis identified polypharmacy to be negatively associated with single-tablet regimens [relative risk reduction (RRR) = 0.48, 95% CI = 0.28-0.81] independently from frailty (RRR = 0.68, 95% CI = 0.59-0.78), after correction for age, gender, HIV infection duration, current and nadir CD4 and calendar year. This association was not found comparing multi-tablet three-drug regimens and less-drug regimens. CONCLUSIONS: Single-tablet regimens are less likely to be prescribed in patients with polypharmacy. Single-tablet regimens are perceived to be less flexible in patients with multi-morbidity and at higher risk of drug-drug interaction.

2017 - Incidence and progression to cirrhosis of new hepatitis C virus infections in persons living with human immunodeficiency virus [Articolo su rivista]
Puoti, M.; Lorenzini, P.; Cozzi-Lepri, A.; Gori, A.; Mastroianni, C.; Rizzardini, G.; Mazzarello, G.; Antinori, A.; d'Arminio Monforte, A.; Girardi, E.; Andreoni, M.; Angarano, G.; Castelli, F.; Cauda, R.; Di Perri, G.; Galli, M.; Iardino, R.; Ippolito, G.; Lazzarin, A.; Perno, C. F.; von Schloesser, F.; Viale, P.; Castagna, A.; Ceccherini-Silberstein, F.; Lo Caputo, S.; Mussini, C.; Ammassari, A.; Balotta, C.; Bandera, A.; Bonfanti, P.; Bonora, S.; Borderi, M.; Calcagno, A.; Calza, L.; Capobianchi, M. R.; Cingolani, A.; Cinque, P.; De Luca, A.; Di Biagio, A.; Gianotti, N.; Guaraldi, G.; Lapadula, G.; Lichtner, M.; Madeddu, G.; Maggiolo, F.; Marchetti, G.; Marcotullio, S.; Monno, L.; Nozza, S.; Quiros Roldan, E.; Rossotti, R.; Rusconi, S.; Santoro, M. M.; Saracino, A.; Zaccarelli, M.; Fanti, I.; Galli, L.; Rodano, A.; Shanyinde, M.; Tavelli, A.; Carletti, F.; Carrara, S.; Di Caro, A.; Graziano, S.; Petrone, F.; Prota, G.; Quartu, S.; Truffa, S.; Giacometti, I. A.; Costantini, A.; Valeriani, C.; Santoro, C.; Suardi, C.; Donati, V.; Verucchi, G.; Minardi, C.; Quirino, T.; Abeli, C.; Manconi, P. E.; Piano, P.; Cacopardo, B.; Celesia, B.; Vecchiet, J.; Falasca, K.; Sighinolfi, L.; Segala, D.; Mazzotta, F.; Vichi, F.; Cassola, G.; Viscoli, C.; Alessandrini, A.; Bobbio, N.; Belvisi, V.; Caramma, I.; Chiodera, A.; Castelli, A. P.; Ridolfo, A. L.; Piolini, R.; Salpietro, S.; Carenzi, L.; Moioli, M. C.; Tincati, C.; Puzzolante, C.; Abrescia, N.; Chirianni, A.; Borgia, G.; Di Martino, F.; Maddaloni, L.; Gentile, I.; Orlando, R.; Baldelli, F.; Francisci, D.; Parruti, G.; Ursini, T.; Magnani, G.; Ursitti, M. A.; Vullo, V.; Cristaudo, A.; Cicalini, S.; Gallo, L.; Nicastri, E.; Acinapura, R.; Capozzi, M.; Libertone, R.; Savinelli, S.; Latini, A.; Iaiani, G.; Fontanelli Sulekova, L.; Cecchetto, M.; Viviani, F.; Mura, M. S.; Rossetti, B.; Caramello, P.; Orofino, G. C.; Sciandra, M.; Bassetti, M.; Londero, A.; Pellizzer, G.; Manfrin, V.; Baldin, G.
abstract

Objective To estimate the incidence of hepatitis C virus (HCV) seroconversion and the risk of severe fibrosis/cirrhosis in HCV seroconverters among persons with human immunodeficiency virus (HIV) infection. Methods We analysed data on 4059 persons with HIV enrolled in a cohort study in Italy. Results Incidence rate of seroconversion was 0.6/100 person-years overall, and drug users and men-who-have-sex-with-men were at highest risk. The cumulative risk of progression to severe fibrosis/cirrhosis was 30% by 10 years after seroconversion. Conclusions New HCV infections have a rapidly progressive course in this population. Persons with HIV and HCV superinfection should be prioritized for treatment with anti-HCV direct-acting antivirals.

2017 - Late presentation increases risk and costs of non-infectious comorbidities in people with HIV: An Italian cost impact study [Articolo su rivista]
Guaraldi, Giovanni; Zona, Stefano; Menozzi, Marianna; Brothers, Thomas D.; Carli, Federica; Stentarelli, Chiara; Dolci, Giovanni; Santoro, Antonella; Da Silva, Ana Rita Domingues; Rossi, Elisa; Falutz, Julian; Mussini, Cristina
abstract

Background: Late presentation (LP) at the time of HIV diagnosis is defined as presentation with AIDS whatever the CD4 cell count or with CD4 <350 cells/mm. The objective of our study was to assess the prevalence of non-infectious comorbidities (NICM) and multimorbidity among HIV-positive individuals with and without a history of LP (HIV + LP and HIV + EP, respectively), and compare them to matched HIV-negative control participants from a community-based cohort. The secondary objective was to provide estimates and determinants of direct cost of medical care in HIV patients. Methods: We performed a matched cohort study including HIV + LP and HIV + EP among people attending the Modena HIV Metabolic Clinic (MHMC) in 2014. HIV-positive participants were matched in a 1:3 ratio with HIV-negative participants from the CINECA ARNO database. Multimorbidity was defined as the concurrent presence of ≥2 NICM. Logistic regression models were constructed to evaluate associated predictors of NICM and multimorbidity. Results: We analyzed 452 HIV + LP and 73 HIV + EP participants in comparison to 1575 HIV-negative controls. The mean age was 46 ± 9 years, 27.5% were women. Prevalence of NICM and multimorbidity were fourfold higher in the HIV + LP compared to the general population (p < 0.001), while HIV + EP present an intermediate risk. LP was associated with increased total costs in all age strata, but appear particularly relevant in patients above 50 years of age, after adjusting for age, multimorbidity, and antiretroviral costs. Conclusions: LP with HIV infection is still very frequent in Italy, is associated with higher prevalence of NICM and multimorbidity, and contributes to higher total care costs. Encouraging early testing and access to care is still urgently needed.

2017 - Lower Frailty Is Associated with Successful Cognitive Aging Among Older Adults with HIV [Articolo su rivista]
Wallace, Lindsay M. K; Ferrara, Maria; Brothers, Thomas D; Garlassi, Sara; Kirkland, Susan A; Theou, Olga; Zona, Stefano; Mussini, Cristina; Moore, David; Rockwood, Kenneth; Guaraldi, Giovanni
abstract

Aging with HIV poses unique and complex challenges, including avoidance of neurocognitive disorder. Our objective here is to identify the prevalence and predictors of successful cognitive aging (SCA) in a sample of older adults with HIV. One hundred three HIV-infected individuals aged 50 and older were recruited from the Modena HIV Metabolic Clinic in Italy. Participants were treated with combination antiretroviral therapy for at least 1 year and had suppressed plasma HIV viral load. SCA was defined as the absence of neurocognitive impairment (as defined by deficits in tasks of episodic learning, information processing speed, executive function, and motor skills) depression, and functional impairment (instrumental activities of daily living). In cross-sectional analyses, odds of SCA were assessed in relation to HIV-related clinical data, HIV-Associated Non-AIDS (HANA) conditions, multimorbidity (≥2HANA conditions), and frailty. A frailty index was calculated as the number of deficits present out of 37 health variables. SCA was identified in 38.8% of participants. Despite no differences in average chronologic age between groups, SCA participants had significantly fewer HANA conditions, a lower frailty index, and were less likely to have hypertension. In addition, hypertension (odds ratio [OR] = 0.40, p = .04), multimorbidity (OR = 0.35, p = .05), and frailty (OR = 0.64, p = .04) were significantly associated with odds of SCA. Frailty is associated with the likelihood of SCA in people living with HIV. This defines an opportunity to apply knowledge from geriatric population research to people aging with HIV to better appreciate the complexity of their health status.

2017 - Metabolic concerns in aging HIV-infected persons: from serum lipid phenotype to fatty liver [Articolo su rivista]
Guaraldi, Giovanni; Lonardo, Amedeo; Maia, Liliana; Palella, Frank J.
abstract

: Among HIV-infected persons, the assessment of nonalcoholic fatty liver disease (NAFLD) provides a window through which overall metabolic health can be evaluated. In this review, we summarize clinical data that support the roles of aging and metabolic dysregulation as factors contributing to fatty liver/NAFLD among HIV-infected persons.Age-related metabolic alterations include hepatic anatomic and functional changes, altered homeostasis of gastrointestinal microbiota and anthropometric changes (such as a shift of body fat depots from the subcutaneous to the visceral compartment) that are often associated with the development of insulin resistance and increased cardiovascular risk.Fatty changes in the liver occur not only with metabolic disruption but also with virus-induced injury. Chronic hepatitis C virus infection is commonly associated with fatty liver, and can be related to both hepatitis C virus genotype and host metabolic features. Similarly, HIV infection is associated with fatty liver as a result of multiple viral and host factors. Clearly, lipodystrophy, dysregulation of the gut-liver axis and HIV infection itself may each contribute simultaneously to NAFLD pathogenesis. Although lifestyle changes are the mainstay of treatment, to date no drug has specifically been approved for use in persons with NAFLD. Moreover, current guidelines provide no specific therapeutic recommendations for persons with NAFLD older than 65 years.Well-designed studies characterizing the epidemiology, pathogenesis, clinical outcomes and potential therapeutic interventions for liver disease and associated metabolic comorbidities in older HIV-infected patients are urgently needed.

2017 - My smart age with HIV: An innovative mobile and IoMT framework for patient's empowerment [Relazione in Atti di Convegno]
Orsini, Mirko; Pacchioni, Marco; Malagoli, Andrea; Guaraldi, Giovanni
abstract

In the My Smart Age with HIV (MySAwH) project1, an innovative mobile and IoMT framework has been developed to empower patients via health promotion, assessing reduction in health deficit and improvement in quality of life. The MySAwH IoMT framework has been designed to expand the traditional healthcare infrastructure providing patient monitoring and support outside the hospitals. It allows the collection of patient's data from smartphone and wearable devices, the integration and analysis of the collected data, and provide real-time insights of patient's health status. Health coaches can monitor the patient's care path and establish a direct communication channel through an integrated secure chat system. This paper describes the MySAwH IoMT framework features and demonstrate how the IoMT, mobile and wearable technologies have been successfully exploited to provide: i) physicians with a continuous patient monitoring to measure the response to illness and the life quality improvement; ii) patients with an up to date insight of health conditions and a constant support via a direct communication with the health coaches.

2017 - Novelties in evaluation and monitoring of human immunodeficiency virus-1 infection: Is standard virological suppression enough for measuring antiretroviral treatment success? [Articolo su rivista]
Svicher, V.; Marchetti, G.; Ammassari, A.; Ceccherini-Silberstein, F.; Sarmati, L.; Andreoni, M.; Angarano, G.; Antinori, A.; Antonelli, G.; Bandera, A.; Bonfanti, P.; Bonora, S.; Borderi, M.; Calcagno, A.; Capobianchi, M. R.; Castagna, A.; Castelli, F.; Cauda, R.; Celesia, B. M.; Chirianni, A.; Cicalini, S.; Cingolani, A.; Cinque, P.; Clementi, M.; Cossarizza, A.; Monforte, A. D.; D'Ettorre, G.; De Luca, A.; Di Biagio, A.; Di Perri, G.; Galli, M.; Gianotti, N.; Girardi, E.; Guaraldi, G.; Lazzarin, A.; Lichtner, M.; Lo Caputo, S.; Madeddu, G.; Maggi, P.; Maggiolo, F.; Marchetti, G. C.; Mastroianni, C.; Mussini, C.; Nozza, S.; Nunnari, G.; Parisi, S.; Parruti, G.; Perno, C. F.; Piconi, S.; Carla, M.; Ripamonti, D.; Rusconi, S.; Santoro, M.; Sterrantino, G.; Svicher, V.; Vullo, V.; Zaccarelli, M.; Zazzi, M.
abstract

The high potency and tolerability of the currently available antiretroviral drugs has modified HIV-1 infection from a life-threatening disease to a chronic illness. Nevertheless, some issues still remain open to optimize the management of HIV-1 infected patients in term of maintenance of virological suppression over time, identifying patients that could benefit from simplification therapy, and reducing co-mordibities driven by chronic inflammation. The availability of robust and affordable virological and immunological markers can help in solving these issues by providing information on the burden of HIV-1 reservoir in all the anatomical compartments in which the virus replicates as well as on persistent inflammation, immune activation and senescence despite successful virological suppression. In this light, this review is aimed at providing new insights (arising from a two-day Italian expert meeting hold in Rome in March 2016) in evaluation and monitoring of HIV-1 infection from a virological, immunological and clinical perspective. Particular attention has been focused on role of novel parameters (such as total HIV-1 DNA, residual viremia, and immunological markers) in optimizing treatment strategies, enhancing medical adherence, and individualizing monitoring.

2017 - Pituitary growth hormone (GH) secretion is partially rescued in HIV-infected patients with GH deficiency (GHD) compared to hypopituitary patients [Articolo su rivista]
Diazzi, Chiara; Brigante, Giulia; Ferrannini, G.; Ansaloni, Anna; Zirilli, Lucia; De Santis, M. C.; Zona, Stefano; Guaraldi, Giovanni; Rochira, Vincenzo
abstract

Biochemical growth hormone deficiency is prevalent among human immunodeficiency virus-infected patients, but if this condition is clinically relevant remains challenging. The aim is to prospectively compare the growth hormone deficiency/insulin-like growth factor-1 status of 71 human immunodeficiency virus-infected patients with impaired growth hormone response to growth hormone releasing hormone + Arginine with that of 65 hypopituitary patients affected by a true growth hormone deficiency secondary to pituitary disease. The main outcomes were: basal serum growth hormone, insulin-like growth factor-1, insulin-like growth factor binding protein 3, growth hormone peak and area under the curve after growth hormone response to growth hormone releasing hormone + Arginine test, body mass index, waist and hip circumference, and body composition by dual energy X-ray absorptiometry. Insulin-like growth factor-1 binding protein 3, basal growth hormone (p < 0.005), growth hormone peak and area under the curve after growth hormone response to growth hormone releasing hormone + Arginine, waist to hip ratio, insulin-like growth factor-1, fasting glucose, insulin, and triglycerides (p < 0.0001) were lower in hypopituitary than human immunodeficiency virus-infected patients. Total and trunk fat mass by dual energy X-ray absorptiometry were higher in hypopituitary than in human immunodeficiency virus-infected patients (p < 0.0001). In all the patients total body fat was associated with both growth hormone peak and area under the curve at stepwise linear regression analysis. The degree of growth hormone deficiency is more severe in hypopituitary than in human immunodeficiency virus-infected patients, suggesting that the function of growth hormone/insulin-like growth factor-1 axis is partially rescued in the latter thanks to a preserved pituitary secretory reserve. Data from the current study suggest that human immunodeficiency virus-infected patients with peak growth hormone < 9 mg/L may have partial growth hormone deficiency and clinicians should be cautious before prescribing recombinant human growth hormone replacement treatment to patients living with human immunodeficiency virus.

2017 - Practical Review of Recognition and Management of Obesity and Lipohypertrophy in HIV Infection [Articolo su rivista]
Lake, Jordan E; Stanley, Takara; Apovian, Caroline; Bhasin, Shalendar; Brown, Todd T; Capeau, Jaqueline; Currier, Judith S; Dube, Michael P; Falutz, Julian; Grinspoon, Steven K; Guaraldi, Giovanni; Martinez, Esteban; Mccomsey, Grace A; Sattler, Fred R; Erlandson, Kristine M.
abstract

Obesity and lipohypertrophy are common in treated HIV infection and contribute to morbidity and mortality among HIV-infected adults on antiretroviral therapy (ART).

2017 - Predictors of transitions in frailty severity and mortality among people aging with HIV [Articolo su rivista]
Brothers, Thomas D.; Kirkland, Susan; Theou, Olga; Zona, Stefano; Malagoli, Andrea; Wallace, Lindsay M. K.; Stentarelli, Chiara; Mussini, Cristina; Falutz, Julian; Guaraldi, Giovanni; Rockwood, Kenneth
abstract

Background: People aging with HIV show variable health trajectories. Our objective was to identify longitudinal predictors of frailty severity and mortality among a group aging with HIV. Methods: Exploratory analyses employing a multistate transition model, with data from the prospective Modena HIV Metabolic Clinic Cohort Study, based in Northern Italy, begun in 2004. Participants were followed over four years from their first available visit. We included all 963 participants (mean age 46.8±7.1; 29% female; 89% undetectable HIV viral load; median current CD4 count 549, IQR 405–720; nadir CD4 count 180, 81–280) with four-year data. Frailty was quantified using a 31-item frailty index. Outcomes were frailty index score or mortality at four-year follow-up. Candidate predictor variables were baseline frailty index score, demographic (age, sex), HIV-disease related (undetectable HIV viral load, current CD4+ T-cell count, nadir CD4 count, duration of HIV infection, and duration of antiretroviral therapy [ARV] exposure), and behavioral factors (smoking, injection drug use (IDU), and hepatitis C virus co-infection). Results: Four-year mortality was 3.0% (n = 29). In multivariable analyses, independent predictors of frailty index at follow-up were baseline frailty index (RR 1.06, 95% CI 1.05–1.07), female sex (RR 0.93, 95% CI 0.87–0.98), nadir CD4 cell count (RR 0.96, 95% CI 0.93–0.99), duration of HIV infection (RR 1.06, 95% CI 1.01–1.12), duration of ARV exposure (RR 1.08, 95% CI 1.02–1.14), and smoking pack-years (1.03, 1.01–1.05). Independent predictors of mortality were baseline frailty index (OR 1.19, 1.02–1.38), current CD4 count (0.34, 0.20–0.60), and IDU (2.89, 1.30–6.42). Conclusions: Demographic, HIV-disease related, and social and behavioral factors appear to confer risk for changes in frailty severity and mortality among people aging with HIV.

2017 - Pregnant with HIV before age 25: data from a large national study in Italy, 2001-2016 [Articolo su rivista]
Floridia, M; Masuelli, G; Tamburrini, E; Cetin, I; Liuzzi, G; Martinelli, P; Guaraldi, Giovanni; Spinillo, A; Vimercati, A; Maso, G; Pinnetti, C; Frisina, V; Dalzero, S; Ravizza, M.
abstract

Young pregnant women with HIV may be at significant risk of unplanned pregnancy, lower treatment coverage, and other adverse pregnancy outcomes. In a large cohort of pregnant women with HIV in Italy, among 2979 pregnancies followed in 2001-2016, 9·0% were in women <25 years, with a significant increase over time (2001-2005: 7·0%; 2006-2010: 9·1%; 2011-2016: 12·2%, P < 0·001). Younger women had a lower rate of planned pregnancy (23·2% vs. 37·7%, odds ratio (OR) 0·50, 95% confidence interval (CI) 0·36-0·69), were more frequently diagnosed with HIV in pregnancy (46·5% vs. 20·9%, OR 3·29, 95% CI 2·54-4·25), and, if already diagnosed with HIV before pregnancy, were less frequently on antiretroviral treatment at conception (<25 years: 56·3%; ⩾25 years: 69·0%, OR 0·58, 95% CI 0·41-0·81). During pregnancy, treatment coverage was almost universal in both age groups (98·5% vs. 99·3%), with no differences in rate of HIV viral suppression at third trimester and adverse pregnancy outcomes. The data show that young women represent a growing proportion of pregnant women with HIV, and are significantly more likely to have unplanned pregnancy, undiagnosed HIV infection, and lower treatment coverage at conception. During pregnancy, antiretroviral treatment, HIV suppression, and pregnancy outcomes are similar compared with older women. Earlier intervention strategies may provide additional benefits in the quality of care for women with HIV.

2017 - Psychological rather than organic and/or relational components are involved in sexual dysfunction in Young/Middle aged human immunodeficiency virus (HIV)-Infected Men. [Abstract in Rivista]
Decaroli, MARIA CHIARA; De Vincentis, Sara; Diazzi, Chiara; Zona, Stefano; Guaraldi, Giovanni; Santi, Daniele; Rochira, Vincenzo
abstract

Background HIV-infection is associated to an increased prevalence of erectile dysfunction (ED). In HIV-infected men ED seems to be less related to serum Testosterone (T), depending from other factors. Aim To investigate the role of different components (organic, relational, psycho- logical) of erectile function by using validate questionnaires in HIV-infected men with normal serum T. Methodology Prospective, cross-sectional, observational study on eugonadal HIV-infected male patients with ongoing Highly Active Antiretroviral Therapy (HAART) attending the Clinic of Infectious Diseases. The International Index of Erectile Function (IIEF)-15, IIEF-5 and Structured Interview for Erectile Dysfunction (SIEDY) were used to assess sexual function. Sexual desire was further evaluated through a direct question during the visit. LC-MS/MS was used to assess gonadal status. Results 225 HIV-infected patients were enrolled (mean age 45.19G5.36 years). SIEDY scores at appendix and scale 3 were significantly higher in patients with ED at IIEF- 15 (nZ136, 60.4%) compared with those without ED (P!0.001 and PZ0.015, respectively). Conversely, scale 1 (PZ0.448) and 2 (PZ0.503) of SIEDY did not differ between patients with or without ED, suggesting a predominance of the psychological basis of ED in our cohort. The erectile function domain at IIEF-15 was directly correlated with IIEF-5 score (0.778, P!0.001). Similarly, the score at SIEDY appendix was significantly different among ED degrees at IIEF-15 (P!0.001). In particular, lower score was found in HIV-infected men without ED compared to those with mild, moderate and severe ED (P!0.001, PZ0.001, and P!0.001, respectively), confirming the reliability of these tools. Sexual desire was impaired in 73 patients (31.33%) at interview with a good correlation with the specific item of IIEF-15 (P!0.001). Conclusions The psychological component impacts in a significant manner on ED in HIV- infection context. Despite the high prevalence of comorbidities in these patients, the organic component does not affect erectile function. All the three validated questionnaires seem to be trustworthy in the diagnosis of ED in this setting.

2017 - Psychological rather than organic and/or relational components are involved in sexual dysfunction in young/middle aged human immunodeficiency virus (HIV)-infected men. [Abstract in Atti di Convegno]
Decaroli, MARIA CHIARA; De Vincentis, Sara; Diazzi, Chiara; Zona, Stefano; Guaraldi, Giovanni; Santi, Daniele; Rochira, Vincenzo
abstract

BACKGROUND: HIV-infection is associated to an increased prevalence of erectile dysfunction (ED). In HIV-infected men ED seems to be less related to serum Testosterone (T), depending from other factors. AIM: To investigate the role of different components (organic, relational, psychological) of erectile function by using validate questionnaires in HIV-infected men with normal serum T. METHODOLOGY: Prospective, cross-sectional, observational study on eugonadal HIV-infected male patients with ongoing Highly Active Antiretroviral Therapy (HAART) attending the Clinic of Infectious Diseases. The International Index of Erectile Function (IIEF)-15, IIEF-5 and Structured Interview for Erectile Dysfunction (SIEDY) were used to assess sexual function. Sexual desire was further evaluated through a direct question during the visit. LC-MS/MS was used to assess gonadal status. RESULTS: 225 HIV-infected patients were enrolled (mean age 45.19±5.36years). SIEDY scores at appendix and scale 3 were significantly higher in patients with ED at IIEF-15 (n=136, 60.4%) compared with those without ED (p<0.001 and p=0.015, respectively). Conversely, scale 1 (p=0.448) and 2 (p=0.503) of SIEDY did not differ between patients with or without ED, suggesting a predominance of the psychological basis of ED in our cohort. The erectile function domain at IIEF-15 was directly correlated with IIEF-5 score (0.778, p<0.001). Similarly, the score at SIEDY appendix was significantly different among ED degrees at IIEF-15 (p<0.001). In particular, lower score was found in HIV-infected men without ED compared to those with mild, moderate and severe ED (p<0.001, p=0.001, and p<0.001, respectively), confirming the reliability of these tools. Sexual desire was impaired in 73 patients (31.33%) at interview with a good correlation with the specific item of IIEF-15 (p<0.001). CONCLUSIONS: The psychological component impacts in a significant manner on ED in HIV-infection context. Despite the high prevalence of comorbidities in these patients, the organic component does not affect erectile function. All the three validated questionnaires seem to be trustworthy in the diagnosis of ED in this setting.

2017 - Rate, correlates and outcomes of repeat pregnancy in HIV-infected women [Articolo su rivista]
Floridia, M.; Tamburrini, E.; Masuelli, G.; Martinelli, P.; Spinillo, A.; Liuzzi, G.; Vimercati, A.; Alberico, S.; Maccabruni, A.; Pinnetti, C.; Frisina, V.; Dalzero, S.; Ravizza, M.; Mori, F.; Ortolani, P.; dalle Nogare, E. R.; Di Lorenzo, F.; Sterrantino, G.; Meli, M.; Polemi, S.; Nocentini, J.; Baldini, M.; Montorzi, G.; Mazzetti, M.; Rogasi, P.; Borchi, B.; Vichi, F.; Del Pin, B.; Pinter, E.; Anzalone, E.; Marocco, R.; Mastroianni, C.; Mercurio, V. S.; Carocci, A.; Grilli, E.; Zaramella, M.; Mariani, B.; Natalini Raponi, G.; Guaraldi, G.; Nardini, G.; Stentarelli, C.; Beghetto, B.; Degli Antoni, A. M.; Molinari, A.; Crisalli, M. P.; Donisi, A.; Piepoli, M.; Cerri, V.; Zuccotti, G.; Giacomet, V.; Coletto, S.; Di Nello, F.; Madia, C.; Placido, G.; Vivarelli, A.; Castelli, P.; Savalli, F.; Portelli, V.; Sabbatini, F.; Francisci, D.; Bernini, L.; Grossi, P.; Rizzi, L.; Maso, G.; Airoud, M.; Soppelsa, G.; Meloni, A.; Dedoni, M.; Cuboni, C.; Ortu, F.; Piano, P.; Citernesi, A.; Bordoni Vicini, I.; Luzi, K.; Roccio, M.; Miccolis, A.; De Gennaro, A.; Guerra, B.; Cervi, F.; Simonazzi, G.; Margarito, E.; Capretti, M. G.; Marsico, C.; Faldella, G.; Sansone, M.; Agangi, A.; Capone, A.; Maruotti, M.; Tibaldi, C.; Trentini, L.; Todros, T.; Cetin, I.; Brambilla, T.; Savasi, V.; Personeni, C.; Giaquinto, C.; Fiscon, M.; Rubino, E.; Bucceri, A.; Matrone, R.; Scaravelli, G.; Genovese, O.; Cafforio, C.; Tozzi, V.; Massetti, P.; Casadei, A. M.; Cavaliere, A. F.; Cellini, M.; Castelli Gattinara, G.; Marconi, A. M.; Sacchi, V.; Ierardi, M.; Polizzi, C.; Mattei, A.; Pirillo, M. F.; Amici, R.; Galluzzo, C. M.; Donnini, S.; Baroncelli, S.; Villani, P.; Cusato, M.; Cerioli, A.; De Martino, M.; Mastroiacovo, P.; Parazzini, F.; Vella, S.
abstract

Objectives: The aim of the study was to assess the rate, determinants, and outcomes of repeat pregnancies in women with HIV infection. Methods: Data from a national study of pregnant women with HIV infection were used. Main outcomes were preterm delivery, low birth weight, CD4 cell count and HIV plasma viral load. Results: The rate of repeat pregnancy among 3007 women was 16.2%. Women with a repeat pregnancy were on average younger than those with a single pregnancy (median age 30 vs. 33 years, respectively), more recently diagnosed with HIV infection (median time since diagnosis 25 vs. 51 months, respectively), and more frequently of foreign origin [odds ratio (OR) 1.36; 95% confidence interval (CI) 1.10–1.68], diagnosed with HIV infection in the current pregnancy (OR: 1.69; 95% CI: 1.35–2.11), and at their first pregnancy (OR: 1.33; 95% CI: 1.06–1.66). In women with sequential pregnancies, compared with the first pregnancy, several outcomes showed a significant improvement in the second pregnancy, with a higher rate of antiretroviral treatment at conception (39.0 vs. 65.4%, respectively), better median maternal weight at the start of pregnancy (60 vs. 61 kg, respectively), a higher rate of end-of-pregnancy undetectable HIV RNA (60.7 vs. 71.6%, respectively), a higher median birth weight (2815 vs. 2885 g, respectively), lower rates of preterm delivery (23.0 vs. 17.7%, respectively) and of low birth weight (23.4 vs. 15.4%, respectively), and a higher median CD4 cell count (+47 cells/μL), with almost no clinical progression to Centers for Disease Control and Prevention stage C (CDC-C) HIV disease (0.3%). The second pregnancy was significantly more likely to end in voluntary termination than the first pregnancy (11.4 vs. 6.1%, respectively). Conclusions: Younger and foreign women were more likely to have a repeat pregnancy; in women with sequential pregnancies, the second pregnancy was characterized by a significant improvement in several outcomes, suggesting that women with HIV infection who desire multiple children may proceed safely and confidently with subsequent pregnancies.

2017 - Role of Normalized T-Cell Subsets in Predicting Comorbidities in a Large Cohort of Geriatric HIV-infected Patient [Articolo su rivista]
Calcagno, A; Piconi, S; Focà, E; Nozza, S; Carli, Federica; Montrucchio, C; Cattelan, A. M; Orofino, G; Celesia, B. M; Morena, V; De Socio, G. V; Guaraldi, Giovanni
abstract

Adults aging with HIV are at greater risk for several comorbidities. The CD4+ cell count and CD4+/CD8+ ratio often fail to normalize in elderly patients despite prolonged antiretroviral therapy; this has been associated with concomitant diseases and poor prognosis.

2017 - Successful Pre- and Posttransplant Sofosbuvir-Based Anti-Hepatitis C Virus Treatment in Persons Living With Human Immunodeficiency Virus Infection [Articolo su rivista]
Guaraldi, Giovanni; Rossotti, Roberto; Verucchi, Gabriella; Tavio, Marcello; Pasulo, Luisa; Beghetto, Barbara; Dolci, Giovanni; Nardini, Giulia; Badia, Lorenzo; Magliano, Anna; Moioli, Maria Cristina; Puoti, Massimo
abstract

This retrospective study reports the data of sofosbuvir-based anti-hepatitis C virus treatment in 24 candidates and 24 recipients of liver transplantation coinfected with human immunodeficiency virus. Sustained virologic response was cumulatively 85% (90% and 100% in those treated with optimal schedules pre- and posttransplant, respectively).

2017 - Switching from a ritonavir-boosted protease inhibitor to a dolutegravir-based regimen for maintenance of HIV viral suppression in patients with high cardiovascular risk [Articolo su rivista]
Gatell, José M; Assoumou, Lambert; Moyle, Graeme; Waters, Laura; Johnson, Margaret; Domingo, Pere; Fox, Julie; Martinez, Esteban; Stellbrink, Hans-Jürgen; Guaraldi, Giovanni; Masia, Mar; Gompels, Mark; De Wit, Stephane; Florence, Eric; Esser, Stefan; Raffi, François; Pozniak, Anton L
abstract

To compare the efficacy, safety, and impact on lipid fractions of switching from a ritonavir-boosted protease inhibitor (PI/r) to a dolutegravir (DTG) regimen.

2017 - Testosterone is poorly related to erectile dysfunction in young/middle aged human immunodeficiency virus-infected men. [Abstract in Rivista]
De Vincentis, Sara; Santi, Daniele; Decaroli, MARIA CHIARA; Fanelli, F.; Mezzullo, M.; Fazzini, A.; Ansaloni, Anna; Pagotto, U.; Guaraldi, Giovanni; Rochira, Vincenzo
abstract

Background human immunodeficiency virus (HIV)-infection is strongly associated to erectile dysfunction (ED) in men. Preliminary data suggests that ED is poorly associated with serum T in HIVC men. Aim To investigate in HIV-infected men the relationship between sexual function as assessed by the validated International Index of Erectile Function (IIEF-15) and T deficiency using Liquid Chromatography-tandem Mass Spectrometry (LC-MS/MS). Methodology Prospective, cross-sectional, observational study on HIV-infected male patients with ongoing Highly Active Antiretroviral Therapy (HAART), attending the Clinic of Infectious Diseases. IIEF-15 and IIEF-5 questionnaires were used to define ED, while LC-MS/MS was used for hormonal assays. Results 233 consecutive HIV-infected patients were enrolled (mean age 45.29G5.33 years). Eight patients (3.4%) had total T !300 ng/dl, while 142 patients (61.5%) had ED (score %25). Age, hormonal data and duration of HIV-infection and HAART did not differ among groups of patients according to the degree of ED. The direct comparison of each ED cluster showed that months of infection were significantly higher in men with severe ED compared to mild ED (PZ0.037). The erectile function domain at IIEF-15 was directly correlated with IIEF-5 score (0.778, P!0.001), as expected. Moreover, the IIEF-15 score was inversely related to months of infection (K0.147, PZ0.026), but not to months of HAART therapy (K0.121, PZ0.071). Conclusions To the best of our knowledge, this is the first, properly-designed prospective study aiming to investigate the relationship between erectile function and serum T, assessed by LC-MS/MS in HIV-infected men. In our cohort, i) IIEF-5 is reliable as IIEF-15 for ED diagnosis, ii) ED is not associated with serum T, iii) erectilef unction is not influenced by T and HAART, but only by HIV-infection duration. In conclusion, several specific factors, such as the duration of HIV infection, are involved in erectile function in HIV-infected men and should be carefully considered in this setting, while hormonal status seems to be less important. DOI: 10.1530/endoabs.49.EP1166

2017 - Testosterone (T) is poorly related to erectile dysfunction (ED) in young/middle aged human immunodeficiency virus (HIV)-infected men. [Abstract in Atti di Convegno]
De Vincentis, Sara; Santi, Daniele; Decaroli, MARIA CHIARA; Fanelli, F.; Mezzullo, M.; Fazzini, A.; Ansaloni, Anna; Pagotto, U.; Guaraldi, Giovanni; Rochira, Vincenzo
abstract

BACKGROUND: HIV-infection is strongly associated to ED in men. Preliminary data suggests that ED is poorly associated with serum T in HIV+ men. AIM: To investigate in HIV-infected men the relationship between sexual function as assessed by the validated International Index of Erectile Function (IIEF-15) and T deficiency using Liquid Chromatography-tandem Mass Spectrometry (LC-MS/MS). METHODOLOGY: Prospective, cross-sectional, observational study on HIV-infected male patients with ongoing Highly Active Antiretroviral Therapy (HAART), attending the Clinic of Infectious Diseases. IIEF-15 and IIEF-5 questionnaires were used to define ED, while LC-MS/MS was used for hormonal assays. RESULTS: 233 consecutive HIV-infected patients were enrolled (mean age 45.29±5.33years). Eight patients (3.4%) had total T <300ng/dL, while 142 patients (61.5%) had ED (score ≤25). Age, hormonal data and duration of HIV-infection and HAART did not differ among groups of patients according to the degree of ED. The direct comparison of each ED cluster showed that months of infection were significantly higher in men with severe ED compared to mild ED (p=0.037). The erectile function domain at IIEF-15 was directly correlated with IIEF-5 score (0.778, p<0.001), as expected. Moreover, the IIEF-15 score was inversely related to months of infection (-0.147, p=0.026), but not to months of HAART therapy (-0.121, p=0.071). CONCLUSIONS: To the best of our knowledge, this is the first, properly-designed prospective study aiming to investigate the relationship between erectile function and serum T, assessed by LC-MS/MS in HIV-infected men. In our cohort, a) IIEF-5 is reliable as IIEF-15 for ED diagnosis, b) ED is not associated with serum T, c) erectile function is not influenced by T and HAART, but only by HIV-infection duration. In conclusion, several specific factors, such as the duration of HIV infection, are involved in erectile function in HIV-infected men and should be carefully considered in this setting, while hormonal status seems to be less important

2016 - An update on heart transplantation in human immunodeficiency virus–infected patients [Articolo su rivista]
Agüero, F.; Castel, M. A.; Cocchi, Stefania; Moreno, A.; Mestres, C. A.; Cervera, C.; Pérez Villa, F.; Tuset, M.; Cartañà, R.; Manzardo, C.; Guaraldi, Giovanni; Gatell, J. M.; Miró, J. M.
abstract

Cardiovascular diseases have become a significant cause of morbidity in patients with human immunodeficiency virus (HIV) infection. Heart transplantation (HT) is a well-established treatment of end-stage heart failure (ESHF) and is performed in selected HIV-infected patients in developed countries. Few data are available on the prognosis of HIV-infected patients undergoing HT in the era of combined antiretroviral therapy (cART) because current evidence is limited to small retrospective cohorts, case series, and case reports. Many HT centers consider HIV infection to be a contraindication for HT; however, in the era of cART, HT recipients with HIV infection seem to achieve satisfactory outcomes without developing HIV-related events. Consequently, selected HIV-infected patients with ESHF who are taking effective cART should be considered candidates for HT. The present review provides epidemiological data on ESHF in HIV-infected patients from all published experience on HT in HIV-infected patients since the beginning of the epidemic. The practical management of these patients is discussed, with emphasis on the challenging issues that must be addressed in the pretransplant (including HIV criteria) and posttransplant periods. Finally, proposals are made for future management and research priorities.

2016 - Antiretroviral treatment in older patients [Capitolo/Saggio]
Guaraldi, G.; Gomes, A. F.; Silva, A. R.
abstract

2016 - Atazanavir/ritonavir monotherapy: 96 week efficacy, safety and bone mineral density from the MODAt randomized trial [Articolo su rivista]
Galli, Laura; Spagnuolo, Vincenzo; Bigoloni, Alba; D'Arminio Monforte, Antonella; Montella, Francesco; Antinori, Andrea; Di Biagio, Antonio; Rusconi, Stefano; Guaraldi, Giovanni; Di Giambenedetto, Simona; Borderi, Marco; Gibellini, Davide; Caramatti, Giada; Lazzarin, Adriano; Castagna, Antonella
abstract

To report the 96 week results on efficacy, safety and bone mineral density (BMD) in subjects with HIV-1 that were virologically suppressed and treated with atazanavir/ritonavir monotherapy versus atazanavir/ritonavir triple therapy.

2016 - Clinical Research Nurse involvement to foster a community based transcultural research in RODAM European study [Articolo su rivista]
Caselgrandi, Agnese; Guaraldi, Giovanni; Cottafavi, Katiuscia; Artioli, Giovanna; Ferri, Paola
abstract

Background and aim of the work: The Clinical Research Nurse (CRN) can be considered the fulcrum of clinical studies, being a vital link between patient, principal investigator, study sponsor and administrative staff. The clinical research’s way is still long and the contribution that CRNs can provide is crucial. In Italy, a CRN was employed in the study: Research on Obesity & Type 2 Diabetes among African Migrants (RODAM). The aim of the paper is to explore and describe the experience of this involvement. Methods: The CRN managed the project in order to gain a complete collaboration from the Ghanaian population. From the first contact, the CRN decided to adopt a transcultural approach with the aim to create a relationship of understanding, mutual trust respect for each other’s cultural diversity. The CRN also used organizational, technical and linguistic skills. Results: The day-to-day trial management from CRN included the following activities: obtaining local Ethics Committee study approval; recruiting the study staff; planning the study activities; identifying potential study participants; collaborating with the mediators; managing contacts with other RODAM centers; conducting a follow-up of patients. The most important results of CRN involvement have been the empowerment of Ghanaian community and the effective healthcare promotion. Conclusions: The project encouraged the Ghanaian community to increase their healthcare awareness and encouraged the Ghanaian population to create new strategies to face the hard health challenges. The CRN is the most versatile and appropriate health professional to deal the entire study.

2016 - Comorbid Conditions and Older Adults with HIV [Capitolo/Saggio]
Guaraldi, G.; Silva, A. R.
abstract

2016 - Curare la malattia da HIV: ritorno al paziente? [Articolo su rivista]
Girardi, Enrico; D’ARMINIO MONFORTE, Antonella; Camoni, Laura; Pezzotti, Patrizio; Guaraldi, Giovanni; Ammassari, Adriana; Antinori, Andrea; Bonora, Stefano; Mussini, Cristina; Cingolani, Antonella; Corbelli, GIULIO MARIA; Adami, Silvia; DEGLI ESPOSTI, Luca; Andretta, Margherita
abstract

Negli ultimi 20 anni la malattia da HIV è an-data progressivamente trasformandosi da una patologia invariabilmente letale a una condizione cronica trattabi-le, grazie alla disponibilità di terapie antiretrovirali sempre più efficaci. Un uso diffuso di queste terapie ha inoltre la potenzialità di contribuire al controllo della diffusione del contagio. È significativamente diminuita nelle persone con HIV l’incidenza di manifestazioni opportunistiche favorite dalla immunodepressione, mentre sono divenute molto più comuni patologie cronico-degenerative, come patolo-gie cardio- e cerebrovascolari, metaboliche, ossee, renali ed epatiche, legate allo stato di infiammazione cronica e all’invecchiamento della popolazione di queste persone. Nel 2030, si prevede che oltre l’80% delle persone con HIV più anziani avrà almeno una patologia cronico-degenerati-va, rispetto al 19% delle persone HIV-negative, e oltre un quarto di essi avrà tre o più patologie. Tra le persone con HIV va incrementandosi la prevalenza di una condizione di fragilità. La scelta delle strategie terapeutiche per la malat-tia da HIV quindi deve oggi essere basata non più soltanto sulla capacità dei farmaci di indurre una completa soppres-sione della replicazione virale nel breve/medio termine. Le scelte terapeutiche devono favorire l’aderenza e l’assenza di tossicità sul lungo termine, avere la capacità di ripristina-re l’omeostasi immunitaria e ridurre quindi l’infiammazione cronica e il rischio di patologie correlate, avere un impatto positivo nel tempo sulle condizioni complessive di vita del-la persona con HIV, misurato anche con indicatori quali i patient related oucomes.

2016 - Discontinuation of initial antiretroviral therapy in clinical practice: Moving toward individualized therapy [Articolo su rivista]
Di Biagio, A.; Cozzi-Lepri, A.; Prinapori, R.; Angarano, G.; Gori, A.; Quirino, T.; De Luca, A.; Costantini, A.; Mussini, C.; Rizzardini, G.; Castagna, A.; Antinori, A.; Monforte, A. D.; Moroni, M.; Andreoni, M.; D'Arminio Monforte, A.; Castelli, F.; Cauda, R.; Di Perri, G.; Galli, M.; Iardino, R.; Ippolito, G.; Lazzarin, A.; Perno, C. F.; Von Schloesser, F.; Viale, P.; Ceccherini-Silberstein, F.; Girardi, E.; Lo Caputo, S.; Puoti, M.; Ammassari, A.; Balotta, C.; Bandera, A.; Bonfanti, P.; Bonora, S.; Borderi, M.; Calcagno, A.; Calza, L.; Capobianchi, M. R.; Cingolani, A.; Cinque, P.; Caputo, N.; Gianotti, N.; Guaraldi, G.; Lapadula, G.; Lichtner, M.; Madeddu, G.; Maggiolo, F.; Marchetti, G.; Marcotullio, S.; Monno, L.; Quiros Roldan, E.; Rossotti, R.; Rusconi, S.; Santoro, M.; Saracino, A.; Zaccarelli, M.; Fanti, I.; Galli, L.; Lorenzini, P.; Rodano, A.; Shanyinde, M.; Tavelli, A.; Giacometti, A.; Mazzoccato, S.; Santoro, C.; Suardi, C.; Vanino, E.; Verucchi, G.; Minardi, C.; Abeli, C.; Manconi, P. E.; Piano, P.; Vecchiet, J.; Falasca, K.; Sighinolfi, L.; Segala, D.; Mazzotta, F.; Alessandrini, A.; Piscopo, R.; Mazzarello, G.; Mastroianni, C.; Belvisi, V.; Caramma, I.; Chiodera, A.; Castelli, A. P.; Ridolfo, A. L.; Piolini, R.; Salpietro, S.; Carenzi, L.; Moioli, M. C.; Tincati, C.; Puzzolante, C.; Abrescia, N.; Chirianni, A.; Borgia, G.; Guida, M. G.; Gargiulo, M.; Gentile, I.; Orlando, R.; Baldelli, F.; Francisci, D.; Parruti, G.; Ursini, T.; Magnani, G.; Ursitti, M. A.; Vullo, V.; D'Avino, A.; Gallo, L.; Nicastri, E.; Acinapura, R.; Capozzi, M.; Libertone, R.; Tebano, G.; Viviani, F.; Sasset, L.; Mura, M. S.; Caramello, P.; Orofino, G. C.; Rossetti, B.; Sciandra, M.; Bassetti, M.; Londero, A.; Pellizzer, G.; Manfrin, V.
abstract

Background: Study aim was to estimate the rate and identify predictors of discontinuation of first combination antiretroviral therapy (cART) in recent years. Methods: Patients who initiated first cART between January 2008 and October 2014 were included. Discontinuation was defined as stop of at least 1 drug of the regimen, regardless of the reason. All causes of discontinuation were evaluated and 3 main endpoints were considered: toxicity, intolerance, and simplification. Predictors of discontinuation were examined separately for all 3 endpoints. Kaplan-Meier analysis was used for the outcome discontinuation of ≥1 drug regardless of the reason. Cox regression analysis was used to identify factors associated with treatment discontinuation because of the 3 reasons considered. Results: A total of 4052 patients were included. Main reason for stopping at least 1 drug were simplification (29%), intolerance (21%), toxicity (19%), other causes (18%), failure (8%), planned discontinuation (4%), and nonadherence (2%). In a multivariable Cox model, predictors of discontinuation for simplification were heterosexual transmission (P = 0.007), being immigrant (P = 0.017), higher nadir lymphocyte T CD4+cell (P = 0.011), and higher lymphocyte T CD8+cell count (P = 0.025); for discontinuation due to intolerance: the use of statins (P = 0.029), higher blood glucose levels (P = 0.050). About toxicity: higher blood glucose levels (P = 0.010) and the use of zidovudine/lamivudine as backbone (P = 0.044). Conclusions: In the late cART era, the main reason for stopping the initial regimen is simplification. This scenario reflects the changes in recommendations aimed to enhance adherence and quality of life, and minimize drug toxicity.

2016 - Emphysema distribution and diffusion capacity predict emphysema progression in human immunodeficiency virus infection [Articolo su rivista]
Leung, Janice M.; Malagoli, Andrea; Santoro, Antonella; Besutti, Giulia; Ligabue, Guido; Scaglioni, Riccardo; Dai, Darlene; Hague, Cameron; Leipsic, Jonathon; Sin, Don D.; Man, S. F. Paul; Guaraldi, Giovanni
abstract

Background Chronic obstructive pulmonary disease (COPD) and emphysema are common amongst patients with human immunodeficiency virus (HIV). We sought to determine the clinical factors that are associated with emphysema progression in HIV. Methods 345 HIV-infected patients enrolled in an outpatient HIV metabolic clinic with ô2 chest computed tomography scans made up the study cohort. Images were qualitatively scored for emphysema based on percentage involvement of the lung. Emphysema progression was defined as any increase in emphysema score over the study period. Univariate analyses of clinical, respiratory, and laboratory data, as well as multivariable logistic regression models, were performed to determine clinical features significantly associated with emphysema progression. Results 17.4% of the cohort were emphysema progressors. Emphysema progression was most strongly associated with having a low baseline diffusion capacity of carbon monoxide (DLCO) and having combination centrilobular and paraseptal emphysema distribution. In adjusted models, the odds ratio (OR) for emphysema progression for every 10% increase in DLCO percent predicted was 0.58 (95% confidence interval [CI] 0.41-0.81). The equivalent OR (95% CI) for centrilobular and paraseptal emphysema distribution was 10.60 (2.93-48.98). Together, these variables had an area under the curve (AUC) statistic of 0.85 for predicting emphysema progression. This was an improvement over the performance of spirometry (forced expiratory volume in 1 second to forced vital capacity ratio), which predicted emphysema progression with an AUC of only 0.65. Conclusion Combined paraseptal and centrilobular emphysema distribution and low DLCO could identify HIV patients who may experience emphysema progression.

2016 - Fatty liver is associated with an increased risk of diabetes and cardiovascular disease-Evidence from three different disease models: NAFLD, HCV and HIV [Articolo su rivista]
Lonardo, Amedeo; Ballestri, Stefano; Guaraldi, Giovanni; Nascimbeni, Fabio; Romagnoli, Dante; Zona, Stefano; Targher, Giovanni
abstract

Fatty liver, which frequently coexists with necroinflammatory and fibrotic changes, may occur in the setting of nonalcoholic fatty liver disease (NAFLD) and chronic infections due to either hepatitis C virus (HCV) or human immunodeficiency virus (HIV). These three pathologic conditions are associated with an increased prevalence and incidence of cardiovascular disease (CVD) and type 2 diabetes (T2D). In this multidisciplinary clinical review, we aim to discuss the ever-expanding wealth of clinical and epidemiological evidence supporting a key role of fatty liver in the development of T2D and CVD in patients with NAFLD and in those with HCV or HIV infections. For each of these three common diseases, the epidemiological features, pathophysiologic mechanisms and clinical implications of the presence of fatty liver in predicting the risk of incident T2D and CVD are examined in depth. Collectively, the data discussed in this updated review, which follows an innovative comparative approach, further reinforce the conclusion that the presence of fatty/inflamed/fibrotic liver might be a shared important determinant for the development of T2D and CVD in patients with NAFLD, HCV or HIV. This review may also open new avenues in the clinical and research arenas and paves the way for the planning of future, well-designed prospective and intervention studies.

2016 - Frailty in HIV [Capitolo/Saggio]
Guaraldi, G.; Brothers, T.
abstract

2016 - HCV-HIV coinfected pregnant women: data from a multicentre study in Italy [Articolo su rivista]
Baroncelli, S.; Pirillo, M. F.; Amici, R.; Tamburrini, E.; Genovese, O.; Ravizza, M.; Maccabruni, A.; Masuelli, G.; Guaraldi, Giovanni; Liuzzi, G.; Pinnetti, C.; Giacomet, V.; Degli Antoni, A.; Vimercati, A.; Dalzero, S.; Sacchi, V.; Floridia, M.
abstract

PURPOSE: To provide information about main pregnancy outcomes in HIV-HCV coinfected women and about the possible interactions between HIV and HCV in this particular population. METHODS: Data from a multicenter observational study of pregnant women with HIV, conducted in Italian University and Hospital Clinics between 2001 and 2015, were used. Eligibility criteria for analysis were HCV coinfection and at least one detectable plasma HCV-RNA viral load measured during pregnancy. Qualitative variables were compared using the Chi-square or the Fisher test and quantitative variables using the Mann-Whitney U test. The Spearman's coefficient was used to evaluate correlations between quantitative variables. RESULTS: Among 105 women with positive HCV-RNA, median HCV viral load was substantially identical at the three trimesters (5.68, 5.45, and 5.86 log IU/ml, respectively), and 85.7 % of the women had at least one HCV-RNA value >5 log IU/ml. Rate of preterm delivery was 28.6 % with HCV-RNA <5 log IU/ml and 43.2 % with HCV-RNA >5log (p = 0.309). Compared to women with term delivery, women with preterm delivery had higher median HCV-RNA levels (third trimester: 6.00 vs. 5.62 log IU/ml, p = 0.037). Third trimester HIV-RNA levels were below 50 copies/ml in 47.7 % of the cases. No cases of vertical HIV transmission occurred. Rate of HCV transmission was 9.0 % and occurred only with HCV-RNA levels >5 log IU/ml. CONCLUSIONS: Coinfection with HIV and HCV has relevant consequences in pregnancy: HIV coinfection is associated with high HCV-RNA levels that might favour HCV transmission, and HCV infection might further increase the risk of preterm delivery in women with HIV. HCV/HIV coinfected women should be considered a population at high risk of adverse outcomes.

2016 - HIV associated Non-AIDS conditions in patients aging with HIV [Capitolo/Saggio]
Guaraldi, G.; Gomes, A. F.; Silva, A. R.
abstract

2016 - Increased risk of virologic failure to the first antiretroviral regimen in HIV-infected migrants compared to natives: Data from the ICONA cohort [Articolo su rivista]
Saracino, A.; Lorenzini, P.; Lo Caputo, S.; Girardi, E.; Castelli, F.; Bonfanti, P.; Rusconi, S.; Caramello, P.; Abrescia, N.; Mussini, C.; Monno, L.; d'Arminio Monforte, A.; Moroni, M.; Andreoni, M.; Angarano, G.; Antinori, A.; Cauda, R.; Di Perri, G.; Galli, M.; Iardino, R.; Ippolito, G.; Lazzarin, A.; Perno, C. F.; von Schloesser, F.; Viale, P.; Castagna, A.; Cozzi-Lepri, A.; Puoti, M.; Ammassari, A.; Balotta, C.; Bonora, S.; Borderi, M.; Capobianchi, M. R.; Ceccherini-Silberstein, F.; Cingolani, A.; Cinque, P.; De Luca, A.; Di Biagio, A.; Gianotti, N.; Gori, A.; Guaraldi, G.; Lapadula, G.; Lichtner, M.; Madeddu, G.; Maggiolo, F.; Marchetti, G.; Marcotullio, S.; Quiros Roldan, E.; Cicconi, P.; Fanti, I.; Galli, L.; Shanyinda, M.; Tavelli, A.; Giacometti, A.; Costantini, A.; Mazzoccato, S.; Santoro, C.; Suardi, C.; Vanino, E.; Verucchi, G.; Minardi, C.; Quirino, T.; Abeli, C.; Manconi, P. E.; Piano, P.; Vecchiet, J.; Falasca, K.; Sighinolfi, L.; Segala, D.; Mazzotta, F.; Cassola, G.; Viscoli, C.; Alessandrini, A.; Piscopo, R.; Mazzarello, G.; Mastroianni, C.; Belvisi, V.; Caramma, I.; Chiodera, A.; Castelli, A. P.; Rizzardini, G.; Ridolfo, A. L.; Piolini, R.; Salpietro, S.; Carenzi, L.; Moioli, M. C.; Tincati, C.; Puzzolante, C.; Chirianni, A.; Borgia, G.; Guida, M. G.; Gargiulo, M.; Gentile, I.; Orlando, R.; Baldelli, F.; Francisci, D.; Parruti, G.; Ursini, T.; Magnani, G.; Ursitti, M. A.; Vullo, V.; d'Avino, A.; Gallo, L.; Nicastri, E.; Acinapura, R.; Capozzi, M.; Libertone, R.; Tebano, 1G.; Zaccarelli, M.; Viviani, F.; Sasset, L.; Mura, M. S.; Rossetti, B.; Orofino, G. C.; Sciandra, M.; Bassetti, M.; Londero, A.; Pellizzer, G.; Manfrin, V.
abstract

Migrant and Italian HIV-infected patients (n = 5773) enrolled in the ICONA cohort in 2004-2014 were compared for disparities in access to an initial antiretroviral regimen and/or risk of virologic failure (VF), and determinants of failure were evaluated. Variables associated with initiating antiretroviral therapy (ART) were analysed. Primary endpoint was time to failure after at least 6 months of ART and was defined as: VF, first of two consecutive virus loads (VL) &gt;200 copies/mL; treatment discontinuation (TD) for any reason; and treatment failure as confirmed VL &gt;200 copies/mL or TD. A Poisson multivariable analysis was performed to control for confounders. Migrants presented significantly lower CD4 counts and more frequent AIDS events at baseline. When adjusting for baseline confounders, migrants presented a lower likelihood to begin ART (odds ratio 0.80, 95% confidence interval (CI) 0.67-0.95, p 0.012). After initiating ART, the incidence VF rate was 6.4 per 100 person-years (95% CI 4.8-8.5) in migrants and 2.7 in natives (95% CI 2.2-3.3). Multivariable analysis confirmed that migrants had a higher risk of VF (incidence rate ratio 1.90, 95% CI 1.25-2.91, p 0.003) and treatment failure (incidence rate ratio 1.16, 95% CI 1.01-1.33, p 0.031), with no differences for TD. Among migrants, variables associated with VF were age, unemployment and use of a boosted protease inhibitor-based regimen versus nonnucleoside reverse transcriptase inhibitors. Despite the use of more potent and safer drugs in the last 10 years, and even in a universal health care setting, migrants living with HIV still present barriers to initiating ART and an increased risk of VF compared to natives.

2016 - Independent association of subclinical coronary artery disease and emphysema in HIV-infected patients [Articolo su rivista]
Besutti, Giulia; Raggi, P.; Zona, Stefano; Scaglioni, Riccardo; Santoro, Antonella; Orlando, Gabriella; Ligabue, Guido; Leipsic, J.; Sin, D. D.; Man, S. F. P.; Guaraldi, Giovanni
abstract

Chronic obstructive pulmonary disease (COPD) and coronary artery disease are inflammatory states with a significant clinical impact. The relationship between them has not been investigated in patients with HIV infection. We assessed the presence of subclinical emphysema and coronary artery disease using chest computed tomography (CT) imaging in a cohort of HIV-infected patients receiving antiretroviral therapy.

2016 - Is Testosterone (T) treatment safe and effective in men with HIV infection? A meta-analysis [Abstract in Rivista]
Santi, Daniele; Guaraldi, Giovanni; Corona, Giovanni; Rochira, Vincenzo
abstract

Background Prevalence of hypogonadism is high (30%) in men with HIV. In these patients T treatment (TT) is currently used mainly to counteract wasting syndrome and/or HIV-related lipodystrophy, irrespective of patients’ serum T. However, its effect and safety in HIV-infected men is still not completely known. Aim To investigate both beneficial and adverse effects related to TT in HIV-infected men using a meta-analytic approach. Methods An extensive MEDLINE search was performed using ‘PubMed’ with the following key-words: ‘HIV’ and: ’hypogonadism’, ‘TT’, ‘T’, ’androgens’ or ‘sex steroids’ from 1946 to April 2015. Meta-analysis included 19 placebo-controlled- clinical trials evaluating TT in HIV patients and was conducted according to PRISMA statement using RevMan. Results All 19 trials evaluated the effect of TT on body weight on a total of 952 subjects (TT group: 557; placebo group: 395). Patients’ gonadal status was often not reported and most of patients were presumably eugonadal. All data are shown as standardized mean and Confidence Interval (CI). TT significantly improved total lean body mass (1.44 [0.82–2.07], P!0.001), total body weight (0.99 [0.25–1.72], PZ0.008) and fat free mass (1.48 [0.85–2.12], P!0.001). This improvement is characterized by higher heterogeneity (I 2Z84%, 88%, and 60%, respectively). Conversely, no beneficial effects were seen on total fat mass (K0.17 [K1.58–1.25], PZ0.820). TT was associated with an increased incidence of minor adverse events (ORZ1.50[1.11–2.01], PZ0.008) and increased mean serum PSA (0.10 ng/mL, [0.03–0.17], PZ0.007). No change in hemoglobin (0.39 g/dL, [K0.29–1.07], PZ0.260) was seen. Conclusions Our study suggests that TT in HIV-infected men is effective in improving body composition (increase in lean body mass), although the incidence of general adverse events is higher than in the placebo group. However, studies show a highest variability and the real benefits of TT in HIV-infected men remains still to be established.

2016 - Kidney Transplantation in HIV-Infected Recipients: Therapeutic Strategy and Outcomes in Monocentric Experience [Articolo su rivista]
Baisi, Alberto; Nava, F.; Baisi, B.; Rubbiani, E.; Guaraldi, Giovanni; DI BENEDETTO, Fabrizio; Giovannoni, M.; Solazzo, A.; Bonucchi, D.; Cappelli, Gianni
abstract

Background In Human immunodeficiency virus (HIV)-positive patients undergoing kidney transplantation, outcomes and immunosuppression (IS) protocol are not yet established due to infectious and neoplastic risks as well as to pharmacokinetic interactions with antiretroviral therapy (TARV). Methods We report a retrospective, 1-center study on 18 HIV+ patients undergoing, between October 2007 and September 2015, kidney transplantation (13 cases) or combined kidney-liver transplant (5 cases). Inclusion criteria for transplant were based on the Italian National Transplant Center protocol. IS regimen was based on quick tapering of steroids and the use of mTOR inhibitors (mTORi) with low dose of calcineurin inhibitors (CNI). In the early post-transplant period, TARV was based on enfuvirtide, raltegravir, plus 1 or more nucleoside analogues. Results In a mean follow-up of 3.1 years, patient survival rate at 1 and 3 years was, respectively, 86.6% and 84.6%, whereas graft survival was 81.2% and 78.6%. Cumulative rejection rate was 20.0% and 26.6% (1- and 3-year results). Median eGFR (MDRD) was 58.8 mL/min and 51.9 mL/min at 1 and 3 years. We had 9 cases of clinically relevant infections (2 Pneumocystis jirovecii pneumonia, 1 pulmonary aspergillosis, 2 severe sepsis, and 4 HCV reactivation) as well as 1 case (5.5%) of HIV reactivation. Conclusions IS therapy based on mTORi and low CNI dose ensures good graft survival, low rate of acute rejection, limited drug toxicity, and control of HIV disease. TARV has no significant interaction with IS therapy.

2016 - Liver Retransplantation in Patients with HIV-1 Infection: An International Multicenter Cohort Study [Articolo su rivista]
Aga¼ero, F.; Rimola, A.; Stock, P.; Grossi, P.; Rockstroh, J. K.; Agarwal, K.; Garzoni, C.; Barcan, L. A.; Maltez, F.; Manzardo, C.; Mari, M.; Ragni, M. V.; Anadol, E.; Di Benedetto, F.; Nishida, S.; Gastaca, M.; Mira, J. M.; Pedreira, J. D.; Castro, M. A.; Lapez, S.; Sua¡rez, F.; Vazquez, P.; Blanch, J.; Brunet, M.; Cervera, C.; de Lazzari, E.; Fondevila, C.; Forner, A.; Fuster, J.; Freixa, N.; GarcA­a-Valdecasas, J. C.; Gil, A.; Gatell, J. M.; Laguno, M.; Marta­nez, M.; Mallolas, J.; Monras, M.; Moreno, A.; Murillas, J.; Paredes, D.; Pacopyrightrez, I.; Torres, F.; Tural, C.; Tuset, M.; Antela, A.; Fernandez, J.; Losada, E.; Varo, E.; Lozano, R.; Araiz, J. J.; Barrao, E.; Letona, S.; Luque, P.; Navarro, A.; Sanjoaqua­n, I.; Serrano, T.; Tejero, E.; Salcedo, M.; BaA+/-ares, R.; Calleja, J.; Berenguer, J.; Cosa­n, J.; Gutiacopyrightrrez, I.; Lapez, J. C.; Miralles, P.; Rama­rez, M.; Rincan, D.; Sanchez, M.; Jimacopyrightnez, M.; de la Cruz, J.; Ferna¡ndez, J. L.; Lozano, J. M.; Santoyo, J.; Rodrigo, J. M.; Sua¡rez, M. A.; Rodra­guez, M.; Alonso, M. P.; Asensi, V.; Gonza¡lez, M. L.; GonzA¡lez-Pinto, I.; Rafecas, A.; Carratala¡, J.; Fabregat, J.; Ferna¡ndez, N.; Xiol, X.; Montejo, M.; Bustamante, J.; Ferna¡ndez, J. R.; Montejo, E.; Ortiz de Urbina, J.; Ruiz, P.; Sua¡rez, M. J.; Testillano, M.; Valdivieso, A.; Ventoso, A.; Abradelo, M.; Costa, J. R.; Fundora, Y.; Jimacopyrightnez, S.; Meneu, J. C.; Moreno, E.; Moreno, V.; Olivares, S. P.; Pacopyrightrez, B.; Pulido, F.; Rubio, R.; Blanes, M.; Aguilera, V.; Berenguer, M.; Lapez, J.; Lapez, R.; Prieto, M.; FariA+/-as, M. C.; Arnaiz, A.; Casafont, F.; Echevarria, S.; Fa¡brega, E.; Garca­a, J. D.; Gamez, M.; Gutiacopyrightrrez, J. M.; Peralta, F. G.; Teira, R.; Moreno, S.; Barcena, R.; Del Campo, S.; Fortaºn, J.; Moreno, A. M.; Torre-Cisneros, J.; Barrera, P.; Camacho, A.; Cantisa¡n, S.; Castan, J. J.; de la Mata, M.; Lara, M. R.; Natera, C.; Rivero, A.; Vidal, E.; Castells, L. I.; Charco, R.; Esteban, J. I.; Gavalda¡, J.; Len, O.; Pahissa, A.; Ribera, E.; Vargas, V.; Pons, J. A.; Cordero, E.; Bernal, C.; Cisneros, J. M.; Gamez, M. A.; Pascasio, J. M.; Rodra­guez, M. J.; Sayazo, M.; Sousa, J. M.; Sua¡rez, G.; Gonza¡lez, J.; Aznar, E.; Barquilla, E.; Esteban, H.; Krahe, L.; Moyano, B.; de la Rosa, G.; Mahillo, B.; Roland, M.; Ascher, N.; Roberts, J.; Freise, C.; Terrault, N.; Carlson, L.; Beatty, G.; Chin-Hong, P.; Dove, L.; Emond, J.; Lobritto, S.; Neu, N.; Yin, M.; Kumar, A.; Ringe, B.; Jacobson, J.; Sass, D.; Diego, J.; Tzakis, A.; Roth, D.; Schiff, E.; Burke, G.; Jayaweera, D.; Olthoff, K.; Blumberg, E.; Bloom, R.; Reddy, R.; Ragni, M.; Shapiro, R.; De Vera, M. E.; Shakil, O.; Simon, D.; Cohen, S. M.; Dodson, S. F.; Jensik, S.; Saltzberg, S.; Stosor, T.; Green, R.; Baker, T.; Gallon, L.; Scarsi, K.; Hanto, D.; Wong, M.; Curry, M.; Johnson, S.; Pavlakis, M.; Barin, B.; Risaliti, A.; Ancarani, F.; Pinna, A. D.; Morelli, C.; Guaraldi, G.; Tarantino, G.; Baccarani, U.; Tavio, M.; Nanni Costa, A.; Beckebaum, S.; Radecke, K.; Bickel, M.; Sterneck, M.; Zoufaly, A.; Ganten, T.; Stoll, M.; Salzberger, B.; Berg, C.; Kittner, J.; O'Grady, J.; Joshi, D.; Heaton, N.; Smud, A.; Genoud, N.; Cahn, F.; Valledor, A.; Gadano, A.; Barcan, L.; Cusini, A.; Rauch, A.; Furrer, H.; Ma¼ller, N. J.; Khanna, N.; van Delden, C.; Oriol, M.; Manata, M. J.; Correia, F.; Machado, J.; Morbey, A.; Glaria, H.; Veloso, J.; Perdigoto, R.; Pereira, P.; Martins, A.; Barroso, E.
abstract

Liver retransplantation is performed in HIV-infected patients, although its outcome is not well known. In an international cohort study (eight countries), 37 (6%; 32 coinfected with hepatitis C virus [HCV] and five with hepatitis B virus [HBV]) of 600 HIV-infected patients who had undergone liver transplant were retransplanted. The main indications for retransplantation were vascular complications (35%), primary graft nonfunction (22%), rejection (19%), and HCV recurrence (13%). Overall, 19 patients (51%) died after retransplantation. Survival at 1, 3, and 5 years was 56%, 51%, and 51%, respectively. Among patients with HCV coinfection, HCV RNA replication status at retransplantation was the only significant prognostic factor. Patients with undetectable versus detectable HCV RNA had a survival probability of 80% versus 39% at 1 year and 80% versus 30% at 3 and 5 years (p = 0.025). Recurrence of hepatitis C was the main cause of death in the latter. Patients with HBV coinfection had survival of 80% at 1, 3, and 5 years after retransplantation. HIV infection was adequately controlled with antiretroviral therapy. In conclusion, liver retransplantation is an acceptable option for HIV-infected patients with HBV or HCV coinfection but undetectable HCV RNA. Retransplantation in patients with HCV replication should be reassessed prospectively in the era of new direct antiviral agents.

2016 - Long-term durability of tenofovir-based antiretroviral therapy In relation to the Co-administration of other drug classes in routine clinical practice [Articolo su rivista]
Costarelli, S.; Cozzi-Lepri, A.; Lapadula, G.; Bonora, S.; Madeddu, G.; Maggiolo, F.; Antinori, A.; Galli, M.; Di Perri, G.; Viale, P.; D'Arminio Monforte, A.; Gori, A.; Moroni, M.; Andreoni, M.; Angarano, G.; Castelli, F.; Cauda, R.; Iardino, R.; Ippolito, G.; Lazzarin, A.; Perno, C. F.; Von Schloesser, F.; Castagna, A.; Ceccherini-Silberstein, F.; Girardi, E.; Lo Caputo, S.; Mussini, C.; Puoti, M.; Ammassari, A.; Balotta, C.; Bonfanti, P.; Borderi, M.; Capobianchi, M. R.; Cingolani, A.; Cinque, P.; De Luca, A.; Di Biagio, A.; Gianotti, N.; Guaraldi, G.; Lichtner, M.; Marchetti, G.; Marcotullio, S.; Monno, L.; Quiros Roldan, E.; Rusconi, S.; Saracino, A.; Cicconi, P.; Fanti, I.; Galli, L.; Lorenzini, P.; Tavelli, A.; Giacometti, A.; Costantini, A.; Mazzoccato, S.; Santoro, C.; Suardi, C.; Vanino, E.; Verucchi, G.; Minardi, C.; Quirino, T.; Abeli, C.; Manconi, P. E.; Piano, P.; Vecchiet, J.; Falasca, K.; Sighinolfi, L.; Segala, D.; Mazzotta, F.; Cassola, G.; Viscoli, C.; Alessandrini, A.; Piscopo, R.; Mazzarello, G.; Mastroianni, C.; Belvisi, V.; Caramma, I.; Chiodera, A.; Castelli, A. P.; Rizzardini, G.; Ridolfo, A. L.; Piolini, R.; Salpietro, S.; Carenzi, L.; Moioli, M. C.; Tincati, C.; Puzzolante, C.; Abrescia, N.; Chirianni, A.; Guida, M. G.; Gargiulo, M.; Baldelli, F.; Francisci, D.; Parruti, G.; Ursini, T.; Magnani, G.; Ursitti, M. A.; Vullo, V.; D'Avino, A.; Gallo, L.; Nicastri, E.; Acinapura, R.; Capozzi, M.; Libertone, R.; Tebano, G.; Cattelan, A.; Sasset, L.; Mura, M. S.; Rossetti, B.; Caramello, P.; Orofino, G. C.; Sciandra, M.; Bassetti, M.; Londero, A.; Pellizzer, G.; Manfrin, V.
abstract

Background: In clinical trials, toxicity leading to tenofovir disoproxil fumarate (TDF) discontinuation is rare (3% by 2 years); however in clinical practice it seems to be higher, particularlywhen TDF is co-administered with ritonavir-boosted protease inhibitors (PI/r). Aims of this study were to assess the rate of TDF discontinuations in clinical practice and to identify factors associated with the risk of stopping TDF. Methods: All antiretroviral treatment (ART)-naive patients initiating a TDF-based regimen were selected from the ICONA Foundation Study cohort. The primary outcome was TDF discontinuation regardless of the reason; secondary outcome measures were TDF discontinuation due to toxicity and selective TDF discontinuation (that is, TDF discontinuation or substitution, maintaining unchanged the remaining antiretroviral treatment). Results: 3,618 ART-naïve patients were included: 54% started a PI/r-based and 46% a NNRTIbased based regimen. Two-hundred-seventy-seven patients discontinued TDF and reintroduced ART within 30 days without TDF. The probability of TDF discontinuation regardless of the reason was of 7.4% (95%CI:6.4-8.5) by 2 years and 14.1% (95%CI:12.2-16.1) by 5 years. The 5-year KM estimates in the PI/r vs. NNRTI group were 20.4% vs. 7.6%, respectively (log-rank p = 0.0001), for the outcome of stopping regardless of the reason, and 10.7% vs. 4.7% (p = 0.0001) for discontinuation due to toxicity. PI/r use and lower eGFR were associated with an increased risk of discontinuing TDF. Conclusion: In our cohort, the frequency of TDF discontinuations was higher than that observed in clinical trials. Co-administration of TDF with PI/r was associated with an increased rate of TDF discontinuations. Further studies are needed to clarify the mechanisms that might have led to this outcome.

2016 - Managing the Older Adult Patient with HIV [Monografia/Trattato scientifico]
Silva, A. R.; Mussi, C.; Falutz, J.; Guaraldi, G.
abstract

This concise, clinically focused pocket guide offers a complete overview of HIV in the older patient and reviews the latest guidelines, treatment options, clinical trials, and management of HIV within this subgroup. The easily accessible text offers infectious disease specialists and other health care professionals with an excellent quick reference tool, with full color tables and figures enhancing the text further. HIV is a chronic disease that affects the immune system, leading to AIDS. As treatments have progressed and patients with HIV are living longer a new aspect has to be taken in to consideration when treating HIV and other conditions. Comorbidities are rife within older adults with HIV, as many of the treatments for HIV cause long-term side effects, such as heart conditions and cancer. Special consideration must be taken to ensure no toxic drug-drug interactions between treatments.

2016 - More than osteoporosis: Age-specific issues in bone health [Articolo su rivista]
Erlandson, Kristine M; Guaraldi, Giovanni; Falutz, Julian
abstract

Purpose of review The interaction between fall and fracture risk factors is an area of increasing clinical relevance, but little information is known about the age-specific issues in bone health unique to HIV-infected adults. The present review will focus on what is known about falls and fall risk factors among HIV-infected adults, and then review the association between decreased muscle, increased adiposity, and frailty with both low bone mineral density (BMD) and falls. Recent findings The rate of falls among middle-aged HIV-infected adults is similar to that of HIV-uninfected adults 65 years and older. Many of the clinical factors that contribute to low BMD overlap with risk factors for falls, resulting in a high risk of a serious fall among older adults with the greatest risk for a fracture. Low muscle mass, increased adiposity and metabolic syndrome, physical function impairment and frailty, common among older HIV-infected adults, contribute to an increased risk for low BMD and falls, and subsequently, may increase the risk of fracture among HIV-infected older adults. Summary Interventions with dual benefit on reducing fall risk and improving BMD are likely to have the greatest impact on fracture prevention in the older, HIV-infected adult.

2016 - Multidimensional geriatric assessment in older patients with HIV [Capitolo/Saggio]
Guaraldi, G.; Falutz, J.
abstract

2016 - Multimorbidity and burden of disease [Capitolo/Saggio]
Brown, Tt; Guaraldi, G
abstract

With effective antiretroviral therapy, HIV has become a chronic disease, and life expectancy among HIV-infected persons is approaching that of HIV-uninfected persons. Despite this success, epidemiologic evidence suggests that the burden of multiple aging-related diseases, including cardiovascular disease, liver disease, metabolic abnormalities, chronic kidney disease, cognitive dysfunction, and osteoporosis, is higher in HIV-infected persons compared to their HIV-uninfected peers. These comorbid diseases tend to cluster in a single person, leading to multimorbidity and polypharmacy. Emerging evidence suggests that multimorbidity among HIV-infected persons results in functional decline, reduced quality of life, and increased mortality. In this review, we examine the epidemiology, risk factors, etiologies, and potential consequences of multimorbidity in aging HIV-infected persons. With aggressive risk factor management for comorbidities and less toxic antiretroviral medications, the burden of multimorbidity in HIV-infected persons can be reduced

2016 - Nonalcoholic fatty liver disease is associated with an almost twofold increased risk of incident type 2 diabetes and metabolic syndrome. Evidence from a systematic review and meta-analysis [Articolo su rivista]
Ballestri, Stefano; Zona, Stefano; Targher, Giovanni; Romagnoli, Dante; Baldelli, Enrica; Nascimbeni, Fabio; Roverato, Alberto; Guaraldi, Giovanni; Lonardo, Amedeo
abstract

Background and Aim:: The magnitude of the risk of incident type 2 diabetes (T2D) and metabolic syndrome (MetS) among patients with nonalcoholic fatty liver disease (NAFLD) is poorly known. We gauged the risk of developing T2D and MetS in patients with NAFLD diagnosed by either serum liver enzymes (aminotransferases or gamma-glutamyltransferase [GGT]) or ultrasonography. Methods:: Pertinent prospective studies were identified through extensive electronic database research, and studies fulfilling enrolment criteria were included in the meta-analysis. Results: Overall, in a pooled population of 117020 patients (from 20 studies), who were followed-up for a median period of 5years (range: 3-14.7years), NAFLD was associated with an increased risk of incident T2D with a pooled relative risk of 1.97 (95% confidence interval [CI], 1.80-2.15) for alanine aminotransferase, 1.58 (95% CI, 1.43-1.74) for aspartate aminotransferase, 1.86 (95% CI, 1.71-2.03) for GGT (last vs first quartile or quintile), and 1.86 (95% CI, 1.76-1.95) for ultrasonography, respectively. Overall, in a pooled population of 81411 patients (from eight studies) who were followed-up for a median period of 4.5years (range: 3-11years), NAFLD was associated with an increased risk of incident MetS with a pooled relative risk of 1.80 (95% CI, 1.72-1.89) for alanine aminotransferase (last vs first quartile or quintile), 1.98 (95% CI, 1.89-2.07) for GGT, and 3.22 (95% CI, 3.05-3.41) for ultrasonography, respectively. Conclusions:: Nonalcoholic fatty liver disease, as diagnosed by either liver enzymes or ultrasonography, significantly increases the risk of incident T2D and MetS over a median 5-year follow-up.

2016 - Nonalcoholic steatohepatitis heralding olmesartan-induced sprue-like enteropathy [Articolo su rivista]
Dolci, Marco; Nascimbeni, Fabio; Romagnoli, Dante; REGGIANI BONETTI, Luca; Guaraldi, Giovanni; Mascia, Maria Teresa; Lonardo, Amedeo
abstract

not available

2016 - Prediction of hard cardiovascular events in HIV patients [Articolo su rivista]
Raggi, Paolo; De Francesco, Davide; Manicardi, Marcella; Zona, Stefano; Bellasi, Antonio; Stentarelli, Chiara; Carli, Federica; Beghetto, Barbara; Mussini, Cristina; Malagoli, Andrea; Guaraldi, Giovanni
abstract

To assess the accuracy of risk prediction algorithms used in the general population and an HIV-specific algorithm to predict hard cardiovascular events.

2016 - Pregnancy outcomes and cytomegalovirus DNAemia in HIV-infected pregnant women with CMV [Articolo su rivista]
Floridia, Marco; Pirillo, Maria F; Antoni, Anna Degli; Molinari, Atim; Tamburrini, Enrica; Pinnetti, Carmela; Guaraldi, Giovanni; Nardini, Giulia; Masuelli, Giulia; Dalzero, Serena; Cetin, Irene; Sansone, Matilde; Amici, Roberta; Ravizza, Marina
abstract

not available

2016 - Psychological, rather than organic and/or relational components are involved in sexual dysfunction in Young/Middle Aged Human immunodeficiency virus (HIV)-Infected Men. [Abstract in Atti di Convegno]
Decaroli, MARIA CHIARA; De Vincentis, Sara; Diazzi, Chiara; Zona, Stefano; Guaraldi, Giovanni; Santi, Daniele; Rochira, Vincenzo
abstract

BACKGROUND: HIV-infection is associated to an increased prevalence of erectile dysfunction (ED)1,2. In HIV- infected men ED seems to be less related to serum Testosterone (T)2-4, ED and sexual dysfunction mainly depending from other factors1,2. However, data on other components of sexual dysfunction in HIV are scanty2. AIM: To investigate the role of different components (organic, relational, psychological) of erectile function by using different validate questionnaire in HIV-infected men with normal serum T who are mainly homosexual (70%). METHODOLOGY: Prospective, cross-sectional, observational study on 225 eugonadal, HIV-infected male patients with ongoing Highly Active Antiretroviral Therapy (HAART) attending the Clinic of Infectious Diseases. The International Index of Erectile Function (IIEF)-15, IIEF-5 and Structured Interview for Erectile Dysfunction (SIEDY) were used for the evaluation of sexual function. Moreover, the sexual desire was further evaluated using a direct question during the visit. Statistical analysis: comparison of continue variables among groups was performed using Kruskal-Wallis test and Dunnet test for post-hoc analyses. RESULTS: 225 HIV-infected patients were enrolled (mean age 45.19±5.36 years) with average duration of HIV- infection and of HAART treatment of 187.62±101.71 and 156.38+89.81 months, respectively. Table 1 summarizes the score obtained in each item evaluated by questionnaires.The SIEDY scores obtained at appendix and scale 3 were significantly higher in patients with ED at IIEF-15 (n=136, 60.4%) compared with those without ED (appendix: 7.64+4.39 vs 4.35+3-14, p&lt;0.001) (scale 3: 2.72+4.39 vs 2.07+1.86, p=0.015). Conversely, scale 1 (2.76+2.16 vs 2.46+2.10, p=0.448) and 2 (0.53+1.02 vs 0.61+1.47, p=0.503) of SIEDY did not differ between patients with or without ED. This suggests that the psychological basis of ED was predominant in HIV-infected men. However, when patients were grouped according to the severity of ED at IIEF-15 all SIEDY items did not differ among the 3 groups (p&gt;0.05). The erectile function domain at IIEF-15 was directly correlated with IIEF-5 score (0.778, p&lt;0.001). Similarly, the score at SIEDY appendix was significantly different among the ED degree found at IIEF-15 (p&lt;0.001). In particular, lower score was found in HIV-infected men without ED compared to those with mild, moderate and severe ED (p&lt;0.001, p=0.001, and p&lt;0.001, respectively), confirming the reliability of these tools. Sexual desire was evaluated using IIEF-15 appropriate domain and during the interview through direct question performed by the clinician. Sexual desire was impaired in 73 patients (31.33%) at interview with a good correlation with the item of IIEF-15 on sexual desire (p&lt;0.001). CONCLUSIONS: The psychological component of ED impacts in a significant manner on ED in men with HIV. Despite the high prevalence of comorbidities in these patients the organic component does not affect erectile function. Similarly, the relational component seems to play a not significant role probably because of the high percentage of men not in a stable relationship. All the three validated questionnaires well describe the degree of erectile dysfunction, with a good correlation index, suggesting that they are all reliable and accurate for the diagnosis of ED in this peculiar population. REFERENCES 1Zona S et al. Erectile dysfunction is more common in young to middle-aged HIV-infected men than in HIV-uninfected men. J Sex Med. 2012 Jul;9(7):1923-30. 2Santi D et al. Male sexual dysfunction and HIV--a clinical perspective. Nat Rev Urol. 2014 Feb;11(2):99-109. 3Rochira V et al. Premature decline of serum total testosterone in HIV-infected men in the HAART-era. PLoS One. 2011;6(12):e28512. 4Rochira V &amp; Guaraldi G. Hypogonadism in the HIV-infected man. Endocrinol Metab Clin North Am. 2014 Sep;43(3):709-30.

2016 - Raltegravir Plus Nevirapine as Maintenance Antiretroviral Therapy in HIV-Positive Patients: Safety, Efficacy and Pharmacokinetics [Articolo su rivista]
Calcagno, A.; Montrucchio, C.; Capetti, A.; Guaraldi, Giovanni; Cenderello, G.; Calza, L.; Lanzafame, M.; Marinaro, L.; Tettoni, M. C.; Trentini, L.; D'Avolio, A.; Di Perri, G.; Bonora, S.
abstract

BACKGROUND: Tolerability, long-term toxicities and selection of resistant variants limit the use and efficacy of antiretroviral drugs in HIV-positive patients. Novel combinations are needed for mantaining long-term control of HIV replication; nevertheless scarse data are available on protease inhibitor-free dual antiretroviral therapies. METHODS: A multi-centric retrospective study was conducted including HIV-1-positive patients on raltegravir/nevirapine dual regimens. Plasma concentrations were measured as therapeutic drug monitoring while a subset of patients underwent intensive 12-hour pharmacokinetic evaluation. RESULTS: A total of 77 patients switching from successful regimens (76.6% male, median age 52 years) was included; 10 patients on raltegravir plus nevirapine once-daily while 67 subjects on twice-daily schedule. After a median follow-up of 32 months 69 patients (89.6%) were still successfully on treatment. Three patients discontinued for side effects (skin rash or hepatoxicity). Virological failure was observed in five patients (6.5%, 3 on once-daily schedule): in 4 patients (80%) resistance-associated mutations were observed (4 reverse transcriptase, 2 integrase). Triglycerides decreased in patients switching with lipid abnormalities (n=52) and estimated creatinine clearance increased in those with less than 60 ml/min (n=13). Median trough raltegravir and nevirapine concentrations were 83 ng/ml (32-227) and 5460 ng/ml (4037-7221); intensive 12-hours pharmacokinetic parameters (n=7) were similar to published data. CONCLUSION: Dual therapy with raltegravir/nevirapine in selected patients was highly effective over a 32-month follow up: virological failure was infrequent (6.5%), most common with once-daily schedule (60%) and often associated with the selection of resistance-associated mutations (80%). Twice-daily raltegravir plus nevirapine deserves further clinical evaluation as an NRTI- and PI-sparing strategy in selected patients.

2016 - Response to first-line ritonavir-boosted protease inhibitors (PI/r)-based regimens in HIV positive patients presenting to care with low CD4 counts: Data from the Icona Foundation Cohort [Articolo su rivista]
D'Arminio Monforte, A.; Cozzi-Lepri, A.; Maggiolo, F.; Rizzardini, G.; Manconi, P. E.; Gianotti, N.; Quirino, T.; Pinnetti, C.; Rusconi, S.; De Luca, A.; Antinori, A.; Andreoni, M.; Angarano, G.; Castelli, F.; Cauda, R.; Di Perri, G.; Galli, M.; Iardino, R.; Ippolito, G.; Lazzarin, A.; Perno, C. F.; Von Schloesser, F.; Viale, P.; Castagna, A.; Ceccherini-Silberstein, F.; Girardi, E.; Lo Caputo, S.; Mussini, C.; Puoti, M.; Ammassari, A.; Balotta, C.; Bandera, A.; Bonfanti, P.; Bonora, S.; Borderi, M.; Calcagno, A.; Calza, L.; Capobianchi, M. R.; Cingolani, A.; Cinque, P.; Di Biagio, A.; Gori, A.; Guaraldi, G.; Lapadula, G.; Lichtner, M.; Madeddu, G.; Marchetti, G.; Marcotullio, S.; Monno, L.; Nozza, S.; Quiros Roldan, E.; Rossotti, R.; Santoro, M. M.; Saracino, A.; Zaccarelli, M.; Fanti, I.; Galli, L.; Lorenzini, P.; Rodano, A.; Shanyinde, M.; Tavelli, A.; Carletti, F.; Carrara, S.; Di Caro, A.; Graziano, S.; Petrone, F.; Prota, G.; Quartu, S.; Truffa, S.; Giacometti, A.; Costantini, A.; Valeriani, C.; Santoro, C.; Suardi, C.; Donati, V.; Verucchi, G.; Minardi, C.; Abeli, C.; Piano, P.; Cacopardo, B.; Celesia, B.; Vecchiet, J.; Falasca, K.; Sighinolfi, L.; Segala, D.; Mazzotta, F.; Vichi, F.; Cassola, G.; Viscoli, C.; Alessandrini, A.; Bobbio, N.; Mazzarello, G.; Mastroianni, C.; Belvisi, V.; Caramma, I.; Chiodera, A.; Castelli, A. P.; Ridolfo, A. L.; Piolini, R.; Salpietro, S.; Carenzi, L.; Moioli, M. C.; Tincati, C.; Puzzolante, C.; Monza, G.; Abrescia, N.; Chirianni, A.; Borgia, G.; Di Martino, F.; Maddaloni, L.; Gentile, I.; Orlando, R.; Baldelli, F.; Francisci, D.; Parruti, G.; Ursini, T.; Magnani, G.; Ursitti, M. A.; Vullo, V.; Cristaudo, A.; Baldin, G.; Cicalini, S.; Gallo, L.; Nicastri, E.; Acinapura, R.; Capozzi, M.; Libertone, R.; Savinelli, S.; Latini, A.; Cecchetto, M.; Viviani, F.; Mura, M. S.; Rossetti, B.; Caramello, P.; Orofino, G. C.; Sciandra, M.; Bassetti, M.; Londero, A.; Pellizzer, G.; Manfrin, V.
abstract

Background There are no data comparing the response to PI/r-based regimens in people presenting for care with low CD4 counts or AIDS (LC). Aim To compare the response to LPV/r-, DRV/r- or ATV/r-based cART regimens in LC initiating cART from ART-naive. Methods We included people enrolled in Icona with either CD4 counts ≤350 cells/mm3 (low CD4-LC) or CD4 counts ≤200 cells/mm3 (very low CD4-VLC) and/or AIDS, starting their first PI/rbased regimen after 2008. Initial regimens were compared by intention-to-treat: i) time to viral failure (VF) (first of 2 consecutive VL&gt;200 copies/mL after ≥6 months); II) time to PI/r discontinuation/switching for any cause (TD) and for toxicity (TDT); III) treatment failure (TF) (VF or TD). Kaplan-Meier and Cox analyses were used. Results 1,362 LC patients were included (DRV/r 607; ATV/r 552; LPV/r 203); 813 VLC. In a median of 18 months (IQR:7-35), the 1-year probability of VF and TF were 2.8% (1.9-3.8) and 21.1% (18.7-23.4). In the adjusted analysis, patients initiating ATV/r had a 53% lower chance, and those initiating DRV/r a 61% lower chance of TD, as compared to LPV/r; the risk of TF was more likely in people starting LPV/r. Results were similar among VLC; in this subgroup LPV/r including regimens demonstrated a lower chance of VF. Conclusions We confirmed in LC a low chance of virological failure by 1 year, with small differences according to PI/r. However, larger differences were observed when comparing longer-term endpoints such as treatment failure. These results are important for people presenting late for care.

2016 - Self-management [Capitolo/Saggio]
Guaraldi, G.; Silva, A. R.
abstract

2016 - Serum total estradiol, but not testosterone is associated with reduced bone mineral density (BMD) in HIV-infected men: a cross-sectional, observational study [Articolo su rivista]
Santi, Daniele; Madeo, Bruno; Carli, Federica; Zona, Stefano; Brigante, Giulia; Vescini, F.; Guaraldi, Giovanni; Rochira, Vincenzo
abstract

By investigating the relationship between serum testosterone, estradiol, and bone mineral density (BMD) in a large cohort of HIV-infected men, estradiol was associated with BMD, relative estrogen deficiency being involved in bone loss in men with hypogonadism, in addition to all HIV-related factors. Increased aromatization in adipose tissue does not counteract HIV-related bone loss. INTRODUCTION: The purpose of this study is to evaluate the relationship between serum testosterone, estradiol, and BMD in a large cohort of HIV-infected men. METHODS: We investigated biochemical, hormonal parameters, and BMD in 1204 HIV-infected men (age 45.64 ± 7.33 years) participating in a cross-sectional, observational study. Among other parameters, the main outcome measures were serum total testosterone and estradiol, gonadotropins, 25-hydroxyvitamin D [25(OH)D], parathormone (PTH), calcium, phosphorous, femoral, and lumbar BMD. RESULTS: In men with HIV, the prevalence of osteoporosis and osteopenia is 15.1 and 63.2 % with 25(OH)D insufficiency being very common (60.1 %). After age adjustment, BMD is positively associated with estradiol, but not testosterone, at linear (p < 0.001) and stepwise (p < 0.05) multiple regression. Lumbar BMD significantly increases across the estradiol quartiles but not among testosterone quartiles. Femoral and lumbar BMD are significantly higher in men with estradiol ≥ 27 pg/mL than in those with estradiol <27 pg/mL. Apart from estradiol, only age, calcium, and BMI predict BMD at stepwise linear multiple regression, but the strength of this association is weak. CONCLUSIONS: Estradiol, but not testosterone, is associated with BMD in HIV-infected men and exerts a protective role on bone especially when it is above 27 pg/mL. Relative estrogen deficiency is a potential mechanism involved in bone loss in hypogonadal HIV-infected men, in addition to all HIV-related factors. Increased aromatization in adipose tissue does not counteract HIV-related bone loss. Finally, reduced BMD in young-to-middle-aged HIV-infected men might be considered a peculiar hallmark of HIV infection due to its relevant prevalence, representing one of the several pieces composing the complicated puzzle of premature aging related to HIV infection.

2016 - Testosterone (T) is poorly related to Erectile Dysfunction (ED) in Young/Middle Aged Human immunodeficiency virus (HIV)-Infected Men. [Abstract in Atti di Convegno]
De Vincentis, Sara; Santi, Daniele; Decaroli, MARIA CHIARA; Fanelli, F.; Mezzullo, M.; Ansaloni, Anna; Pagotto, U.; Guaraldi, Giovanni; Rochira, Vincenzo
abstract

BACKGROUND: HIV infection is strongly associated to ED in men1,2. Preliminary data suggests that ED is poorly associated with serum T in HIV+ men1,3-4. AIM: To investigate the relationship between sexual function as assessed by the validated International Index of Erectile Function (IIEF-15) and T deficiency in HIV-infected men by assessing circulating T by Liquid Chromatography tandem Mass Spectrometry (LC-MS/MS). METHODOLOGY: Prospective, cross-sectional, observational study on 233 consecutive HIV-infected male patients with ongoing Highly Active Antiretroviral Therapy (HAART), attending the Clinic of Infectious Diseases. IIEF-15 questionnaire was used to define patients having ED (score <25), IIEF-5 was performed to check if it is reliable as IIEF-15 in this setting, while LC-MS/MS was used for hormonal assays. Statistical analysis: Continuous and categorical variables were compared using ANOVA univariate and Chi-Square test, respectively. Correlations were performed using Spearman’s Rho coefficient. RESULTS: 233 HIV-infected patients were enrolled (mean age 45.29±5.33 years) with average duration of HIV-infection of 195.98±129.54 months. Eight patients (3.4%) had hypogonadism, defined as total T serum levels below 300 ng/dL. 142 patients (61.5%) had ED (EF score ≤25) (Table 1). Age, hormonal data and duration of HIV infection and HAART did not differ among groups of patients according to the degree of ED (Table 1). Although no differences were seen among categories, the direct comparison of each ED cluster showed that months of infection were significantly higher in men with severe ED compared to mild ED (p=0.037); moreover, men with severe ED had lower T levels than men with mild form (p=0.029). All hypogonadal men had erectile dysfunction (p=0.020). However, no differences were found among ED degree for hypogonadal men (p=0.151). The erectile function domain at IIEF-15 was directly correlated with IIEF-5 score (0.778, p<0.001), as expected. Moreover, the IIEF-15 score was inversely related to months of infection (-0.147, p=0.026) (Figure 1), but not to months of HAART therapy (-0.121, p=0.071). Total T showed an inverse relation with months of infection (-0.172, p=0.009) (Figure 1) and months of HAART (-0.173, p=0.010), but not with IIEF-15 score (0.039; p=0.559). CONCLUSIONS: To the best of our knowledge, this is the first, properly-designed prospective study aiming to investigate the relationship between erectile function and serum T, assessed using the LC-MS/MS in HIV-infected men. Similarly to the IIEF-15, the IIEF-5 recognize ED patients and the scores of both correlates each other. In our cohort, the prevalence of ED and hypogonadism was 61% and 3.4%, respectively. Thus, ED evaluated by IIEF-15 seems to be not directly related to serum total T, but it correlates with age and months of infection. In conclusion, in HIV-infected patients a) IIEF-5 is reliable as IIEF- 15 for ED diagnosis, b) ED is not associated with serum T, c) erectile function is not influenced by T and HAART, but only by HIV-infection duration. In conclusion, several specific factors, such as the duration of HIV infection, are involved in erectile function in HIV-infected men and should be carefully considered in this setting, while hormonal status seems to be less important.

2016 - The PNPLA3 Genetic Variant rs738409 Influences the Progression to Cirrhosis in HIV/Hepatitis C Virus Coinfected Patients [Articolo su rivista]
Núñez Torres, Rocío; Macías, Juan; Mancebo, María; Frías, Mario; Dolci, Giovanni; Téllez, Francisco; Merino, Dolores; Merchante, Nicolás; Gómez Mateos, Jesús; Guaraldi, Giovanni; Rivero Juárez, Antonio; Pineda, Juan A; Real, Luis M.
abstract

Contradictory data about the impact of the rs738409 steatosis-related polymorphism within PNPLA3 gene on liver fibrosis progression in HIV/hepatitis C virus (HIV/HCV)-coinfected patients have been reported. Our objective was to test whether this, and other polymorphisms previously related to fatty liver disease in HIV infection linked to SAMM50 or LPPR4 genes, influence liver fibrosis progression in HIV/HCV-coinfected individuals. Three hundred and thirty two HIV/HCV-coinfected patients who consecutively attended four Spanish university hospitals from November 2011 to July 2013 were included. A liver stiffness cut-off of 14.6 kPa, as determined by transient elastography, was used to diagnose cirrhosis. Liver stiffness progression was studied in 171 individuals who had two available LS determinations without anti-HCV treatment between them. Moreover, 28 HIV/HCV-coinfected patients who underwent liver transplant, as well as 19 non-cirrhotic coinfected individuals used as controls, were included in an additional study. Only rs738409 was associated with cirrhosis: 45 (29.6%) of 152 G allele carriers versus 36 (20.0%) of 180 CC carriers showed cirrhosis (multivariate p = 0.018; adjusted odds ratio = 1.98; 95% confidence interval = 1.12-3.50). Also, 21 (30.4%) of 69 G allele carriers versus 16 (15.7%) of 102 CC patients showed significant liver stiffness progression (adjusted p-value = 0.015; adjusted odds ratio = 2.89; 95% confidence interval = 1.23-6.83). Finally, the proportion of rs738409 G allele carriers was significantly higher in transplanted individuals than in controls (p = 0.044, odds ratio = 3.43; 95% confidence interval = 1.01-11.70). Our results strongly suggest that the rs738409 polymorphism is associated with liver fibrosis progression in HIV/HCV-coinfected patients.

2016 - The transition from co-morbidities to geriatric syndromes in HIV. [Articolo su rivista]
Guaraldi, Giovanni
abstract

Several recent cohort studies have suggested that life expectancy of HIV-infected individuals is currently comparable to that of the general population, particularly when antiretroviral therapy (ART) was initiated at earlier disease stages.1 Simultaneously, HIV seroconversion among older age persons is increasingly recognized, in part as the result of lower perceptions of sexual risk in older people.2 The overall effect is one of advancing age among HIV-infected persons, with a recognition that persons who age with HIV infection have an increased burden of age-related comorbid illnesses compared to persons of a similar age who were more recently HIV-infected.

2016 - Th1 and Th17 pro-inflammatory profile characterizes iNKT cells in virologically suppressed HIV+ patients with low CD4/CD8 ratio [Articolo su rivista]
DE BIASI, Sara; Bianchini, Elena; Nasi, Milena; Digaetano, Margherita; Gibellini, Lara; Carnevale, Gianluca; Borghi, Vanni; Guaraldi, Giovanni; Pinti, Marcello; Mussini, Cristina; Cossarizza, Andrea
abstract

INTRODUCTION:: Scanty data exist on the phenotype and functionality of invariant natural killer T (iNKT) cells in HIV+ patients (pts). METHODS:: By flow cytometry, we studied iNKT cells from 54 HIV+ pts who started combined antiretroviral therapy (cART) and had undetectable viral load for &gt;1 year. Twenty-five maintained a CD4/CD8 ratio &lt;0.4, while 29 reached a ratio &gt;1.1; 32 age- and sex-matched subjects were healthy controls (CTR). RESULTS:: Pts with low ratio had lower percentage of CD4+ iNKT cells compared to pts with high ratio, and higher CD8+ iNKT cell percentage; double negative (DN) iNKT cells were lower in HIV+ pts compared to CTR. Pts with low ratio had higher percentage of CD4+ and DN iNKT cells expressing CD38 and HLA-DR compared to pts with high ratio. CD4+ iNKT cells expressing PD-1 were higher in pts with CD4/CD8 ratio &lt;0.4, while DN iNKT cells expressing PD-1 were lower compared to pts with ratio &gt;1.1. Pts with low ratio had higher CD4+ iNKT cells producing IL-17, CD8+ iNKT cells producing IFN-γ, TNF-α or IFN-γ plus TNF-α, and DN iNKT cells producing IL-17 or IL-17 plus IFN-γ compared to CTR. Activated CD4+ (or CD8+) T cells correlated with activated CD4+ (or CD8+) iNKT cells, as well as the percentages of CD4+ (or CD8+) T cells expressing PD-1 was correlated to that of CD4+ (or CD8+) iNKT cells expressing PD-1. CONCLUSIONS:: Low CD4/CD8 ratio despite effective cART is associated with altered iNKT cell subsets, enhanced activation and prominent Th1/Th17 pro-inflammatory profile.

2016 - Treatment of severe recurrent hepatitis C after liver transplantation in HIV infected patients using sofosbuvir-based therapy [Articolo su rivista]
Campos Varela, I.; Moreno, A.; Morbey, A.; Guaraldi, Giovanni; Hasson, H.; Bhamidimarri, K. R.; Castells, L.; Grewal, P.; Baños, I.; Bellot, P.; Brainard, D. M.; Mchutchison, J. G.; Terrault, N. A.
abstract

Background For liver transplant recipients with hepatitis C virus (HCV) and human immunodeficiency virus (HIV) co-infection, recurrence after LT is associated with a higher risk of graft loss than for HCV mono-infected patients. Prior HCV treatment options were limited by side effects and drug-drug interactions. Aim To evaluate treatment outcomes with sofosbuvir (SOF)-based therapy among HIV/HCV coinfected liver transplant recipients. Methods Access to SOF and ribavirin (RBV) prior to regulatory approval was attained via an international compassionate access program for transplant recipients with a life expectancy of 1 year or less in the absence of HCV treatment. This report focuses on the short and longer term outcomes in HCV-HIV co-infected liver transplant recipients. Results Twenty patients were treated, nine with early severe recurrence and 11 with cirrhosis. Eleven patients received SOF and RBV, one SOF, RBV and Peg-interferon, three SOF, RBV and simeprevir and five SOF, RBV and daclatasvir. Of the 18 patients who completed treatment, 16 (89%) achieved sustained virological response 12 weeks after the end of treatment (SVR12). Liver function tests (including bilirubin and albumin) improved significantly over time. Nineteen serious adverse events occurred in eight (40%) patients, none of them related to SOF. Two patients died during treatment and another, 1 year after the end of therapy, due to progressive end-stage liver disease. Importantly, HIV suppression was not compromised. No significant drug-drug interactions were reported. Conclusions Sofosbuvir-based regimens are safe, well-tolerated and provide high rates of SVR in HCV-HIV co-infected patients with severe recurrence after-liver transplant.

2016 - Triglyceride/HDL ratio and its impact on the risk of diabetes mellitus development during ART [Articolo su rivista]
Squillace, N.; Lorenzini, P.; Lapadula, G.; Bandera, A.; Cozzi-Lepri, A.; Rusconi, S.; Puoti, M.; Castagna, A.; Antinori, A.; Gori, A.; D'Arminio Monforte, A.; Moroni, M.; Andreoni, M.; Angarano, G.; Castelli, F.; Cauda, R.; Di Perri, G.; Galli, M.; Iardino, R.; Ippolito, G.; Lazzarin, A.; Perno, C. F.; Von Schloesser, F.; Viale, P.; Ceccherini-Silberstein, F.; Cozzi-Lepri, A.; Girardi, E.; Lo Caputo, S.; Mussini, C.; Andreoni, M.; Ammassari, A.; Balotta, C.; Bonfanti, P.; Bonora, S.; Borderi, M.; Capobianchi, M. R.; Ceccherini-Silberstein, F.; Cingolani, A.; Cinque, P.; Cozzi-Lepri, A.; De Luca, A.; Di Biagio, A.; Girardi, E.; Gianotti, N.; Gori, A.; Guaraldi, G.; Lichtner, M.; Madeddu, G.; Maggiolo, F.; Marchetti, G.; Marcotullio, S.; Monno, L.; Roldan, E. Q.; Saracino, A.; Cozzi-Lepri, A.; Cicconi, P.; Fanti, I.; Galli, L.; Lorenzini, P.; Rodano, A.; Shanyinda, M.; Tavell, i. A.; Giacometti, A.; Costantini, A.; Mazzoccato, S.; Angarano, G.; Monno, L.; Santoro, C.; Maggiolo, F.; Suardi, C.; Viale, P.; Vanino, E.; Verucchi, G.; Resi, F.; Minardi, C.; Quirino, T.; Abeli, C.; Manconi, P. E.; Piano, P.; Vecchiet, J.; Falasca, K.; Sighinolfi, L.; Segala, D.; Mazzotta, F.; Cassola, G.; Viscoli, C.; Alessandrini, A.; Piscopo, R.; Mazzarello, G.; Mastroianni, C.; Belvisi, V.; Caramma, I.; Chiodera, A.; Dtelli, S.; Galli, M.; Lazzarin, A.; Rizzardini, G.; Ridolfo, A. L.; Piolini, R.; Salpietro, S.; Carenzi, L.; Moioli, M. C.; Tincati, C.; Puzzolante, C.; Gori, A.; Abrescia, N.; Chirianni, A.; Borgia, G.; Guida, M. G.; Gargiulo, M.; Gentile, I.; Orlando, R.; Baldelli, F.; Francisci, D.; Parruti, G.; Ursini, T.; Magnani, G.; Ursitti, M. A.; Cauda, R.; Wendreoni, Q.; Qtinoria, A.; Vullo, V.; Cingolani, A.; D'Avino, A.; Gallo, L.; Nicastri, E.; Acinapura, R.; Capozzi, M.; Libertone, R.; Tebano, G.; Zaccarelli, M.; Viviani, F.; Sasset, L.; Mura, M. S.; Madeddu, G.; De Luca, A.; Rossetti, B.; Caramello, P.; Orofino, G. C.; Bonora, S.; Sciandra, M.; Bassetti, M.; Londero, A.; Pellizzer, G.; Manfrin, V.
abstract

Objectives: Our primary aim was to study diabetes mellitus (DM) arising during combination ART (cART) and to attempt to identify associations between these cases and triglycerides (TRG) and the TRG to HDL-cholesterol (TRG/HDL) ratio. Our secondary aim was to analyse the association between DM development and hepatic fibrosis. Methods: This was a retrospective cohort study. Patients from the Icona Foundation study initiating first-line cART between 1997 and 2013 were selected and observed until new-onset DM or most recent clinical follow-up. The predictive value of TRG and TRG/HDL ratio levels on DM was evaluated using multivariable Poisson regression models. Results: Three-thousand, five-hundred and forty-six patients (males, 73.7%; median age, 38 years; median BMI, 23.1 kg/m2; and hepatitis C virus antibody positive, 22.1%) were included. Of these, 80 developed DM over 13 911 person-years of follow-up (PYFU), corresponding to 5.7 cases per 1000 PYFU (95% CI = 4.6-7.1). At multivariable analysis, latest TRG/HDL ratio, when high, was associated with significant increases in DM risk [relative risk (RR) = 1.63; 95% CI = 1.32-2.01 per 10 points higher], while current TRG, in contrast, was associated with new-onset DM only at crude analysis. Advanced liver fibrosis (defined as fibrosis-4 index &gt;3.25) was also shown to be an independent risk factor for DM (RR = 2.91; 95% CI = 1.10-7.72). Conclusions: High TRG/HDL ratio predicted risk of new-onset DM, independently of other traditional risk factors. Furthermore, our findings suggest that advanced hepatic fibrosis, estimated using the fibrosis-4 score, could provide an additional predictor for DM.

2015 - A frailty index predicts survival and incident multimorbidity independent of markers of HIV disease severity [Articolo su rivista]
Guaraldi, Giovanni; Brothers, Thomas D.; Zona, Stefano; Stentarelli, Chiara; Carli, Federica; Malagoli, Andrea; Santoro, Antonella; Menozzi, Marianna; Mussi, Chiara; Mussini, Cristina; Kirkland, Susan; Falutz, Julian; Rockwood, Kenneth
abstract

Objectives: Aging with HIV is associated with multisystem vulnerability that might be well characterized by frailty. We sought to construct a frailty index based on health deficit accumulation in a large HIV clinical cohort and evaluate its validity including the ability to predict mortality and incident multimorbidity. Design and methods: This is an analysis of data from the prospective Modena HIV Metabolic Clinic cohort, 2004–2014. Routine health variables were screened for potential inclusion in a frailty index. Content, construct, and criterion validity of the frailty index were assessed. Multivariable regression models were built to investigate the ability of the frailty index to predict survival and incident multimorbidity (at least two chronic disease diagnoses) after adjusting for known HIV-related and behavioral factors. Results: Two thousand, seven hundred and twenty participants (mean age 46!8; 32% women) provided 9784 study visits; 37 non-HIV-related variables were included in a frailty index. The frailty index exhibited expected characteristics and met validation criteria. Predictors of survival were frailty index (0.1 increment, adjusted hazard ratio 1.63, 95% confidence interval 1.05–2.52), current CD4þ cell count (0.48, 0.32–0.72), and injection drug use (2.51, 1.16–5.44). Predictors of incident multimorbidity were frailty index (adjusted incident rate ratio 1.98, 1.65–2.36), age (1.07, 1.05–1.09), female sex (0.61, 0.40–0.91), and current CD4þ cell count (0.71, 0.59–0.85). Conclusion: Among people aging with HIV in northern Italy, a frailty index based on deficit accumulation predicted survival and incident multimorbidity independently of HIV-related and behavioral risk factors. The frailty index holds potential value in quantifying vulnerability among people aging with HIV.

2015 - Active HCV replication is associated with incident and prevalent type 2 diabetes in persons living with HIV. [Abstract in Rivista]
Guaraldi, Giovanni
abstract

In HIV-infected individuals metabolic alterations are more prevalent and some antiretroviral drugs may favour type 2 diabetes (T2D). HCV and CMV infections have been associated with T2D in the HIV-negative population. It is not clear whether HCV replication or other factor associated with HCV-antibody + status play a role in determing T2D. We investigated whether HCV and CMV co-infections were associated with incident and prevalent T2D in HIV+ patients from the ICONA cohort

2015 - Aging with HIV vs. HIV Seroconversion at Older Age: A Diverse Population with Distinct Comorbidity Profiles [Articolo su rivista]
Guaraldi, Giovanni; Zona, Stefano; Brothers, Thomas D; Carli, Federica; Stentarelli, Chiara; Dolci, Giovanni; Santoro, Antonella; Beghetto, Barbara; Menozzi, Marianna; Mussini, Cristina; Falutz, Julian
abstract

People aging with HIV might have different health conditions compared with people who seroconverted at older ages. The study objective was to assess the prevalence of, and risk factors for, individual co-morbidities and multimorbidity (MM) between HIV-positive patients with a longer duration of HIV infection, and patients who seroconverted at an older age. We compared estimates across both groups to a matched community-based cohort sampled from the general population.

2015 - American College of Cardiology pooled equations and DAD algorithm to predict freedom from cardiovascular events in HIV patients [Abstract in Rivista]
Guaraldi, Giovanni; De Francesco, D; Malagoli, Andrea; Manicardi, Marcella; Zona, Stefano; Stentarelli, Chiara; Carli, Federica; Santoro, Antonella; Raggi, P.
abstract

A predicted low cardiovascular (CV) risk may be informative in choosing antiretroviral therapy. We compared the 10-year and the 5-year CV risk prediction of the Frammingham Risk Score with the new pooled equations and the new DAD risk score, respectively, to identify patients with low probability of CV disease.

2015 - An update on integrase inhibitors: new opportunities for a personalized therapy? The NEXTaim Project [Articolo su rivista]
Andreoni, Massimo; Marcotullio, Simone; Puro, Vincenzo; De Carli, Gabriella; Tambussi, Giuseppe; Nozza, Silvia; Gori, Andrea; Rusconi, Stefano; Santoro, Maria Mercedes; Clementi, Massimo; Perno, Carlo Federico; d’Arminio Monforte, Antonella; Maggiolo, Franco; Castagna, Antonella; De Luca, Andrea; Galli, Massimo; Giacomelli, Andrea; Borderi, Marco; Guaraldi, Giovanni; Calcagno, Andrea; Di Perri, Giovanni; Bonora, Stefano; Mussini, Cristina; Di Biagio, Antonio; Puoti, Massimo; Bruno, Raffaele; Zuccaro, Valentina; Antinori, Andrea; Cinque, Paola; Croce, Davide; Restelli, Umberto; Rizzardini, Giuliano; Lazzarin, Adriano
abstract

Thanks to the development of antiretroviral agents to control HIV replication, HIV infection has turned from a fatal disease into a treatable chronic infection. The present work collects the opinions of several experts on the efficacy and safety of recently approved second generation of integrase inhibitors and, in particular, on the role of this new class of drugs in antiretroviral therapy. The availability of new therapeutic options represents an opportunity to ameliorate the efficacy of cART in controlling HIV replication also within viral reservoirs. The personalization of the treatment driven mainly by the management of comorbidities, HIV-HCV co-infections and aging, will be easier with antiretroviral drugs without drug-drug interactions and with a better toxicity and tolerability profile. Future assessment of economic impact for the introduction of new innovative drugs in the field of antiretroviral therapy will likely need some degree of adjustment of the evaluation criteria of costs and benefit which are currently based almost exclusively on morbidity and mortality.

2015 - Analysis of inflammasomes and antiviral sensing components reveals decreased expression of NLRX1 in HIV-positive patients assuming efficient antiretroviral therapy [Articolo su rivista]
Nasi, Milena; DE BIASI, Sara; Bianchini, Elena; Digaetano, Margherita; Pinti, Marcello; Gibellini, Lara; Pecorini, Simone; Carnevale, Gianluca; Guaraldi, Giovanni; Borghi, Vanni; Mussini, Cristina; Cossarizza, Andrea
abstract

Objective: Few studies have investigated the importance of different components of the inflammasome system and of innate mitochondrial sensing (IMS) pathways in HIV infection and its treatment. We analysed the expression of several components of the inflammasome and of the IMS in HIV-positive patients taking successful combination antiretroviral therapy (cART). Methods: We enrolled 20 HIV-positive patients under cART, who achieved viral suppression since at least 10 months and 20 age and sex-matched healthy donors. By RT-PCR, using peripheral blood mononuclear cells (PBMCs), we quantified the mRNA expression of 16 genes involved in inflammasome activation and regulation (AIM2, NAIP, PYCARD, CASP1, CASP5, NLRP6, NLRP1, NLRP3, TXNIP, BCL2, NLRC4, PANX1, P2RX7, IL-18, IL-1β, SUGT1) and eight genes involved in IMS (MFN2, MFN1, cGAS, RIG-I, MAVS, NLRX1, RAB32, STING). Results: Compared with controls, HIV-positive patients showed significantly lower mRNA levels of the mitochondrial protein NLRX1, which plays a key role in regulating apoptotic cell death; main PBMC subpopulations behave in a similar manner. No differences were observed in the expression of inflammasome components, which however showed complex correlations. Conclusion: The decreased level of NLRX1 in HIV infection could suggest that the virus is able to downregulate mechanisms linked to triggering of cell death in several immune cell types. The fact that HIV-positive patients did not show altered expression of inflammasome components, nor of most genes involved in IMS, suggests that the infection and/or the chronic immune activation does not influence the transcriptional machinery of innate mechanisms able to trigger inflammation at different levels.

2015 - Automic Function Tests and Pulse wave velocity in HIV Disease: correlation to vascular ageing. [Abstract in Rivista]
Manicardi, Marcella; Guaraldi, P; Santoro, Antonella; Lattanzi, A; Malagoli, Andrea; Salvi, P; Grillo, A; Rossi, Rosario; Mussini, Cristina; Raggi, P; Cortelli, P; Guaraldi, Giovanni
abstract

Autonomic dysfunction is related to increased cardiovascular disease and mortality, being responsible of both subclinical coronary artery disease and cardiac arhythmias. In addition augmented sympathetic activity arises vascular constriction contributing to parietal arterial stiffness. Arterial stiffness can be assessed by measuring the velocity of the initial pulse wave propagation between two sites measured with PulsePen tonometer. We assessed whether subclinical autonomic dysfunction, as evaluated by a complete battery of autonomic function tests, correlates with pulse wave velocity change over 10 year follow up.

2015 - Cardiovascular disease in human immunodeficiency virus infected patients: A true or perceived risk? [Articolo su rivista]
Shahbaz, Shima; Manicardi, Marcella; Guaraldi, Giovanni; Raggi, Paolo
abstract

After the successful introduction of highly active antiretroviral agents the survival of patients infected with the human immunodeficiency virus (HIV) in developed countries has increased substantially. This has allowed the surfacing of several chronic diseases among which cardiovascular disease (CVD) is prominent. The pathogenesis of CVD in HIV is complex and involves a combination of traditional and HIV related factors. An accurate assessment of risk of CVD in these patients is still elusive and as a consequence the most appropriate preventive and therapeutic interventions remain controversial.

2015 - CD4/CD8 ratio normalisation and non-AIDS-related events in individuals with HIV who achieve viral load suppression with antiretroviral therapy: An observational cohort study [Articolo su rivista]
Mussini, Cristina; Lorenzini, Patrizia; Cozzi-Lepri, Alessandro; Lapadula, Giuseppe; Marchetti, Giulia; Nicastri, Emanuele; Cingolani, Antonella; Lichtner, Miriam; Antinori, Andrea; Gori, Andrea; Monforte, Antonella d'Arminio; Moroni, M.; Andreoni, M.; Angarano, G.; Antinori, A.; d'Arminio Monforte, A.; Castelli, F.; Cauda, R.; Di Perri, G.; Galli, M.; Iardino, R.; Ippolito, G.; Lazzarin, A.; Perno, C. F.; von Schloesser, F.; Viale, P.; d'Arminio Monforte, A.; Antinori, A.; Castagna, A.; Ceccherini-Silberstein, F.; Cozzi-Lepri, A.; Girardi, E.; Lo Caputo, S.; Mussini, C.; Puoti, M.; Ammassari, A.; Antinori, A.; d'Arminio Monforte, A.; Balotta, C.; Bonfanti, P.; Bonora, S.; Borderi, M.; Capobianchi, M. R.; Castagna, A.; Ceccherini-Silberstein, F.; Cingolani, A.; Cinque, P.; Cozzi-Lepri, A.; d'Arminio Monforte, A.; De Luca, A.; Di Biagio, A.; Girardi, E.; Gianotti, N.; Gori, A.; Guaraldi, G.; Lapadula, G.; Lichtner, M.; Lo Caputo, S.; Madeddu, Giordano; Maggiolo, F.; Marchetti, G.; Marcotullio, S.; Monno, L.; Mussini, C.; Puoti, M.; Quiros Roldan, E.; Rusconi, S.; Saracino, Gloria Anna Ada; Cozzi-Lepri, A.; Cicconi, P.; Fanti Galli, I.; Lorenzini, P.; Tavelli, A.; Giacometti, A.; Costantini, Alberto; Mazzoccato, S.; Angarano, G.; Monno, L.; Santoro, C.; Maggiolo, F.; Suardi, C.; Viale, P.; Vanino, E.; Verucchi, G.; Castelli, F.; Minardi, C.; Quirino, T.; Abeli, C.; E Manconi, P.; Piano, P.; Vecchiet, J.; Falasca, K.; Sighinolfi, L.; Segala, D.; Mazzotta, F.; Lo Caputo, S.; Cassola, G.; Viscoli, C.; Alessandrini, A.; Piscopo, R.; Mazzarello, G.; Mastroianni, C.; Belvisi, V.; Caramma, I.; Chiodera, A.; Castelli, A. P.; Galli, M.; Lazzarin, A.; Rizzardini, G.; Puoti, M.; d'Arminio Monforte, A.; Ridolfo, A. L.; Piolini, R.; Castagna, A.; Salpietro, S.; Carenzi, L.; Moioli, M. C.; Tincati, C.; Marchetti, G.; Mussini, C.; Puzzolante, C.; Gori, A.; Lapadula, G.; Abrescia, N.; Chirianni, A.; Guida, M. G.; Gargiulo, M.; Baldelli, F.; Francisci, D.; Parruti, G.; Ursini, T.; Magnani, G.; Ursitti, M. A.; Andreoni, M.; Antinori, A.; Vullo, V.; Cingolani, A.; D'Avino, A.; Gallo, Luigi; Nicastri, E.; Acinapura, R.; Capozzi, M.; Libertone, R.; Tebano, G.; Cattelan, A.; Sasset, L.; Mura, M. S.; De Luca, A.; Rossetti, B.; Caramello, P.; Di Perri, G.; Orofino, G. C.; Bonora, Sara; Sciandra, M.; Bassetti, M.; Londero, A.; Pellizzer, G.; Manfrin, V.
abstract

Background: In patients with HIV, immune reconstitution after antiretroviral therapy (ART) is often incomplete. We assessed the probability of patients reaching a CD4/CD8 ratio of 1 or more after the start of ART and its association with the onset of non-AIDS-defining events and death. Methods: We did an analysis of the ICONA cohort, which recruited treatment-naive patients with HIV in Italy. We included participants in the cohort who started ART, reached an undetectable viral load (≤80 copies per mL), and had a CD4/CD8 ratio of less than 0·8 at the time of an undetectable viral load. We defined ratio normalisation in patients as two consecutive values of 1 or more. We used Kaplan-Meier curves to estimate the cumulative probability of ratio normalisation. We then used Poisson regression models to identify factors independently associated with normalisation and with progression to non-AIDS-defining events or death. Findings: We included 3236 participants, enrolled between Jan 22, 1997, and Feb 25, 2013. At the start of ART, median CD4/CD8 ratio in our population was 0·39 (IQR 0·26-0·55). 458 (14%) patients reached a CD4/CD8 ratio of 1 or more; the estimated probability of normalisation was 4·4% (95% CI 3·7-5·2) by 1 year from baseline, 11·5% (10·2-13·0) by 2 years, and 29·4% (26·7-32·4) by 5 years. Factors associated with normalisation were high pre-ART CD4 cell counts, a high CD4/CD8 ratio at baseline, and negative cytomegalovirus serological findings. The incidence rate of non-AIDS-defining events for patients with a CD4/CD8 ratio of less than 0·30 (4·2 per 100 patient-years, 95% CI 3·4-5·3) was double that for those with a ratio of 0·30-0·45 (2·3, 2·1-2·5) or more than 0·45 (2·2, 1·7-2·9). A ratio of less than 0·30 was independently associated with an increased risk of non-AIDS-defining events or death compared with one of more than 0·45. Interpretation: Few patients had normalised CD4/CD8 ratios, even though they had viral suppression. Low ratios were associated with increased risk of serious events and deaths. The CD4/CD8 ratio could be used by clinicians to identity patients at risk of non-AIDS-related events. Funding: AbbVie, Bristol-Myers Squibb, Gilead, Janssen, Merck Sharp &amp; Dohme, ViiV Italy.

2015 - Changes with menopause in the distribution of frailty index (FI) in HIV infected women. [Abstract in Rivista]
Zona, Stefano; Brothers, T; Malagoli, Andrea; Menozzi, Marianna; Carli, Federica; Stentarelli, Chiara; Wallace, L; Theou, O; Kirkland, S; Mussini, Cristina; Rockwood, K; Guaraldi, Giovanni
abstract

Menopause is a physiological aging transition associated with rapid metabolic and physical changes. The aim of this study was to describe changes with menopause in the longitudinal distributions of a frailty index in HIV infected women.

2015 - Consequences of presentation with advanced HIV disease in pregnancy: data from a national study in Italy [Articolo su rivista]
Floridia, Marco; Tamburrini, Enrica; Masuelli, Giulia; Guaraldi, Giovanni; Molinari, Atim; Cetin, Irene; Dalzero, Serena; Spinillo, Arsenio; Liuzzi, Giuseppina; Pinnetti, Carmela; Vicini, Ilaria; Castelli, Paula; Sacchi, Valentina; Ravizza, Marina
abstract

Among 469 women with a diagnosis of HIV in pregnancy, 74 (15.8%) presented with less than 200 CD4 cells per cubic millimeter. The only variable significantly associated with this occurrence was African origin (odds ratio: 2.22, 95% confidence intervals: 1.32 to 3.75, P = 0.003). Four women with low CD4 (5.6%), compared with none with higher CD4 counts, had severe AIDS-defining conditions (P < 0.001) during pregnancy or soon after delivery, and one transmitted HIV to the newborn. Early preterm delivery (<32 weeks) was significantly more frequent with low CD4 (6.2% vs. 1.4%, P = 0.015). An earlier access to HIV testing, particularly among immigrants of African origin, can prevent severe HIV-related morbidity.

2015 - Cytomegalovirus coinfection is associated with an increased risk of severe non-AIDS-defining events in a large cohort of HIV-infected patients [Articolo su rivista]
Moroni, M.; Angarano, G.; Antinori, A.; Armignacco, O.; Castelli, F.; Cauda, R.; Di Perri, G.; Galli, M.; Iardino, R.; Ippolito, G.; Lazzarin, A.; Perno, C. F.; Von Schloesser, F.; Viale, P.; Castagna, A.; Ceccherini-Silberstein, F.; Cozzi-Lepri, A.; Girardi, E.; Caputo, S. L.; Mussini, C.; Puoti, M.; Andreoni, M.; Ammassari, A.; Balotta, C.; Bonfanti, P.; Bonora, S.; Borderi, M.; Capobianchi, M. R.; Cingolani, A.; Cinque, P.; De Luca, A.; Di Biagio, A.; Gianotti, N.; Gori, A.; Guaraldi, G.; Lapadula, G.; Lichtner, M.; Madeddu, G.; Maggiolo, F.; Marchetti, G.; Marcotullio, S.; Monno, L.; Roldan, E. Q.; Rusconi, S.; Fanti, I.; Formenti, T.; Galli, L.; Lorenzini, P.; Giacometti, A.; Costantini, A.; Carrisa, C.; Suardi, C.; Vanino, E.; Verucchi, G.; Minardi, C.; Quirino, T.; Abeli, C.; Manconi, P. E.; Piano, P.; Vecchiet, J.; Falasca, K.; Sighinolfi, L.; Segala, D.; Mazzotta, F.; Cassola, G.; Viscoli, G.; Alessandrini, A.; Piscopo, R.; Mazzarello, G.; Mastroianni, C.; Belvisi, V.; Caramma, I.; Castelli, A. P.; Rizzardini, G.; Monforte, A. D.; Ridolfo, A. L.; Piolini, R.; Salpietro, S.; Carenzi, L.; Moioli, M.; Cicconi, P.; Puzzolante, C.; Abrescia, N.; Chirianni, A.; Guida, M. G.; Gargiulo, M.; Baldelli, F.; Francisci, D.; Parruti, G.; Ursini, T.; Magnani, G.; Ursitti, M. A.; Vullo, V.; D'Avino, A.; Gallo, L.; Nicastri, E.; Acinapura, R.; Capozzi, M.; Libertone, R.; Tebano, G.; Cattelan, A.; Mura, M. S.; Caramello, P.; Orofino, G. C.; Sciandra, M.; Pellizzer, G.; Manfrin, V.; Vita, S.; Saracino, A.
abstract

Background. Chronic cytomegalovirus (CMV) infection has been associated with immunosenescence and immunoactivation in the general population. In human immunodeficiency virus type 1 (HIV-1)-infected people, CMV coinfection, in addition to residual HIV replication and microbial translocation, has been proposed as a key factor in sustaining immune activation, even in individuals with a controlled HIV load. Methods. Patients from the ICONA Study with at least 1 CMV immunoglobulin G (IgG) test available without active CMV disease were included in the analysis. AIDS-defining event or AIDS-related death and severe non- AIDS-defining event or non-AIDS-related death were taken as clinical progression end points. Independent predictors of CMV were identified by multivariable logistic regression. Probabilities of reaching the end points were estimated by survival analyses. Results. A total of 6111 subjects were included, of whom 5119 (83.3%) were CMV IgG positive at baseline. Patients with CMV IgG positivity at baseline were more likely to develop a severe non-AIDS-defining event/ non-AIDS-related death (adjusted hazard ratio [HR], 1.53 [95% confidence interval {CI}, 1.08-2.16]. In particular, CMV seropositivity was an independent risk factor for cardiovascular and cerebrovascular diseases (adjusted HR, 2.27 [95% CI, .97-5.32]). Conclusions. In our study population, CMV/HIV coinfection was associated with the risk of severe non- AIDS-defining events/non-AIDS-related death, especially with cardiovascular and cerebrovascular events, independently of other prognostic factors. This finding supports a potential independent role of CMV coinfection in vascular/degenerative organ disorders in HIV-infected subjects.

2015 - Development and Validation of a Risk Score for Chronic Kidney Disease in HIV Infection Using Prospective Cohort Data from the D:A:D Study [Articolo su rivista]
Mocroft, A.; Lundgren, J. D.; Ross, M.; Law, M.; Reiss, P.; Kirk, O.; Smith, C.; Wentworth, D.; Neuhaus, J.; Fux, C. A.; Moranne, O.; Morlat, P.; Johnson, M. A.; Ryom, L.; Powderly, B.; Shortman, N.; Moecklinghoff, C.; Reilly, G.; Franquet, X.; Sabin, C. A.; Phillips, A.; Weber, R.; Pradier, C.; d'Arminio Monforte, A.; Dabis, F.; El-Sadr, W. M.; De Wit, S.; Kamara, D.; Tverland, J.; Mansfeld, M.; Nielsen, J.; Raben, D.; Salbol Brandt, R.; Rickenbach, M.; Fanti, I.; Krum, E.; Hillebregt, M.; Geffard, S.; Sundstrom, A.; Delforge, M.; Fontas, E.; Torres, F.; Mcmanus, H.; Wright, S.; Kjaer, J.; Sjol, A.; Meidahl, P.; Helweg-Larsen, J.; Schmidt Iversen, J.; Kesselring, A. M.; Friis-Moller, N.; Kowalska, J.; Sabin, C.; Bruyand, M.; Kamara, D. A.; Bower, M.; Fatkenheuer, G.; Donald, A.; Grulich, A.; Prins, J. M.; Kuijpers, T. W.; Scherpbier, H. J.; van der Meer, J. T. M.; Wit, F. W. M. N.; Godfried, M. H.; van der Poll, T.; Nellen, F. J. B.; Geerlings, S. E.; van Vugt, M.; Pajkrt, D.; Bos, J. C.; Wiersinga, W. J.; van der Valk, M.; Goorhuis, A.; Hovius, J. W.; van Eden, J.; Henderiks, A.; van Hes, A. M. H.; Mutschelknauss, M.; Nobel, H. E.; Pijnappel, F. J. J.; Westerman, A. M.; Jurriaans, S.; Back, N. K. T.; Zaaijer, H. L.; Berkhout, B.; Cornelissen, M. T. E.; Schinkel, C. J.; Thomas, X. V.; van den Berge, M.; Stegeman, A.; Baas, S.; Hage de Looff, L.; Versteeg, D.; Pronk, M. J. H.; Ammerlaan, H. S. M.; Korsten-Vorstermans, E. M. H. M.; de Munnik, E. S.; Jansz, A. R.; Tjhie, J.; Wegdam, M. C. A.; Deiman, B.; Scharnhorst, V.; van der Plas, A.; Weijsenfeld, A. M.; van der Ende, M. E.; de Vries-Sluijs, T. E. M. S.; C. M. van Gorp, E.; Schurink, C. A. M.; Nouwen, J. L.; Verbon, A.; Rijnders, B. J. A.; Bax, H. I.; Hassing, R. J.; van der Feltz, M.; Bassant, N.; van Beek, J. E. A.; Vriesde, M.; van Zonneveld, L. M.; de Oude-Lubbers, A.; van den Berg-Cameron, H. J.; Bruinsma-Broekman, F. B.; de Groot, J.; de Zeeuw- de Man, M.; Broekhoven-Kruijne, M. J.; Schutten, M.; Osterhaus, A. D. M. E.; Boucher, C. A. B.; Driessen, G. J. A.; van Rossum, A. M. C.; van der Knaap, L. C.; Visser, E.; Branger, J.; H. M. Duijf-van de Ven C., J.; Schippers, E. F.; van Nieuwkoop, C.; Brimicombe, R. W.; van IJperen, J. M.; van der Hut, G.; Franck, P. F. H.; van Eeden, A.; Brokking, W.; Groot, M.; Damen, M.; Kwa, I. S.; Groeneveld, P. H. P.; Bouwhuis, J. W.; van den Berg, J. F.; van Hulzen, A. G. W.; van der Bliek, G. L.; Bor, P. C. J.; Bloembergen, P.; Wolfhagen, M. J. H. M.; Ruijs, G. J. H. M.; van Lelyveld, S. F. L.; Soetekouw, R.; Hulshoff, N.; van der Prijt, L. M. M.; Schoemaker, M.; Bermon, N.; van der Reijden, W. A.; Jansen, R.; Herpers, B. L.; Veenendaal, D.; Kroon, F. P.; Arend, S. M.; de Boer, M. G. J.; Bauer, M. P.; Jolink, H.; Vollaard, A. M.; Dorama, W.; Moons, C.; Claas, E. C. J.; Kroes, A. C. M.; den Hollander, J. G.; Pogany, K.; Kastelijns, M.; Smit, J. V.; Smit, E.; Bezemer, M.; van Niekerk, T.; Pontesilli, O.; Lowe, S. H.; Oude Lashof, A.; Posthouwer, D.; Ackens, R. P.; Schippers, J.; Vergoossen, R.; Weijenberg Maes, B.; Savelkoul, P. H. M.; Loo, I. H.; Weijer, S.; El Moussaoui, R.; Heitmuller, M.; Kortmann, W.; van Twillert, G.; Cohen Stuart, J. W. T.; Diederen, B. M. W.; Pronk, D.; van Truijen-Oud, F. A.; Leyten, E. M. S.; Gelinck, L. B. S.; van Hartingsveld, A.; Meerkerk, C.; Wildenbeest, G. S.; Mutsaers, J. A. E. M.; Jansen, C. L.; van Vonderen, M. G. A.; van Houte, D. P. F.; Dijkstra, K.; Faber, S.; Weel, J.; Kootstra, G. J.; Delsing, C. E.; van der Burg-van de Plas, M.; Heins, H.; Lucas, E.; Brinkman, K.; Frissen, P. H. J.; Blok, W. L.; Schouten, W. E. M.; Bosma, A. S.; Brouwer, C. J.; Geerders, G. F.; Hoeksema, K.; Kleene, M. J.; van der Meche, I. B.; Toonen, A. J. M.; Wijnands, S.; van Ogtrop, M. L.; Koopmans, P. P.; Keuter, M.; van der Ven, A. J. A. M.; ter Hofstede, H. J. M.; Dofferhoff, A. S. M.; van Crevel, R.; Albers, M.; Bosch, M. E. W.; Grintjes-Huisman, K. J. T.; Zomer, B. J.; Stelma, F. F.; Burger, D.; Richter, C.; van der Berg
abstract

Chronic kidney disease (CKD) is a major health issue for HIV-positive individuals, associated with increased morbidity and mortality. Development and implementation of a risk score model for CKD would allow comparison of the risks and benefits of adding potentially nephrotoxic antiretrovirals to a treatment regimen and would identify those at greatest risk of CKD. The aims of this study were to develop a simple, externally validated, and widely applicable long-term risk score model for CKD in HIV-positive individuals that can guide decision making in clinical practice. A total of 17,954 HIV-positive individuals from the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study with ≥3 estimated glomerular filtration rate (eGFR) values after 1 January 2004 were included. Baseline was defined as the first eGFR &gt; 60 ml/min/1.73 m2 after 1 January 2004; individuals with exposure to tenofovir, atazanavir, atazanavir/ritonavir, lopinavir/ritonavir, other boosted protease inhibitors before baseline were excluded. CKD was defined as confirmed (&gt;3 mo apart) eGFR ≤ 60 ml/min/1.73 m2. Poisson regression was used to develop a risk score, externally validated on two independent cohorts. In the D:A:D study, 641 individuals developed CKD during 103,185 person-years of follow-up (PYFU; incidence 6.2/1,000 PYFU, 95% CI 5.7–6.7; median follow-up 6.1 y, range 0.3–9.1 y). Older age, intravenous drug use, hepatitis C coinfection, lower baseline eGFR, female gender, lower CD4 count nadir, hypertension, diabetes, and cardiovascular disease (CVD) predicted CKD. The adjusted incidence rate ratios of these nine categorical variables were scaled and summed to create the risk score. The median risk score at baseline was −2 (interquartile range –4 to 2). There was a 1:393 chance of developing CKD in the next 5 y in the low risk group (risk score &lt; 0, 33 events), rising to 1:47 and 1:6 in the medium (risk score 0–4, 103 events) and high risk groups (risk score ≥ 5, 505 events), respectively. Number needed to harm (NNTH) at 5 y when starting unboosted atazanavir or lopinavir/ritonavir among those with a low risk score was 1,702 (95% CI 1,166–3,367); NNTH was 202 (95% CI 159–278) and 21 (95% CI 19–23), respectively, for those with a medium and high risk score. NNTH was 739 (95% CI 506–1462), 88 (95% CI 69–121), and 9 (95% CI 8–10) for those with a low, medium, and high risk score, respectively, starting tenofovir, atazanavir/ritonavir, or another boosted protease inhibitor. The Royal Free Hospital Clinic Cohort included 2,548 individuals, of whom 94 individuals developed CKD (3.7%) during 18,376 PYFU (median follow-up 7.4 y, range 0.3–12.7 y). Of 2,013 individuals included from the SMART/ESPRIT control arms, 32 individuals developed CKD (1.6%) during 8,452 PYFU (median follow-up 4.1 y, range 0.6–8.1 y). External validation showed that the risk score predicted well in these cohorts. Limitations of this study included limited data on race and no information on proteinuria. Both traditional and HIV-related risk factors were predictive of CKD. These factors were used to develop a risk score for CKD in HIV infection, externally validated, that has direct clinical relevance for patients and clinicians to weigh the benefits of certain antiretrovirals against the risk of CKD and to identify those at greatest risk of CKD.

2015 - Dissociation of aortic pulse wave velocity from risk factors for cardiovascular disease other than hypertension and age: a prospective study on frailty in HIV-infected patients. [Abstract in Rivista]
Guaraldi, Giovanni; Malagoli, Andrea; Manicardi, Marcella; Grillo, A; Santoro, Antonella; Lattanzi, A; Rossi, Rosario; Mussini, Cristina; Raggi, P; Salvi, P.
abstract

Pulse Wave Velocity (PWV) is a measure of arterial stiffness (arteriosclerosis) and vascular ageing. Both in cross-sectional and prospective studies it was a predictor of cardiovascular disease (CVD)events independent of traditional risk factors for artherosclerosis. CVD is an increasing cause of morbidity and mortality among HIV-infected patients: traditional and non-traditional risk factors are involved. We hypothesized that factors influencing PWV may measure biological ageing in these patients. Therefore we aimed to identify predictors of PWV change over time in HIV-infected patients on stable antiretroviral therapy.

2015 - Epicardial adipose tissue and coronary artery calcium predict incident myocardial infarction and death in HIV-infected patients [Articolo su rivista]
Raggi, Paolo; Zona, Stefano; Scaglioni, Riccardo; Stentarelli, Chiara; Ligabue, Guido; Besutti, Giulia; Menozzi, Marianna; Santoro, Antonella; Malagoli, Andrea; Bellasi, Antonio; Guaraldi, Giovanni
abstract

Epicardial adipose tissue (EAT) and coronary artery calcium (CAC) have been associated with incident coronary artery disease (CAD) and all-cause mortality in the general population. Their prognostic impact in HIV is unknown.

2015 - Evaluation of the prognostic value of impaired renal function on clinical progression in a large cohort of HIV-infected people seen for care in Italy [Articolo su rivista]
Bandera, A.; Gori, A.; Sabbatini, F.; Madeddu, G.; Bonora, S.; Libertone, R.; Mastroianni, C.; Bonfanti, P.; Monforte, A. D.; Cozzi-Lepri, A.; Giacometti, A.; Costantini, A.; Mazzoccato, S.; Angarano, G.; Monno, L.; Santoro, C.; Maggiolo, F.; Suardi, C.; Viale, P.; Borderi, M.; Vanino, E.; Verucchi, G.; Castelli, F.; Roldan, E. Q.; Minardi, C.; Quirino, T.; Abeli, C.; Manconi, P. E.; Piano, P.; Vecchiet, J.; Falasca, K.; Sighinolfi, L.; Segala, D.; Mazzotta, F.; Lo Caputo, S.; Cassola, G.; Viscoli, C.; Di Biagio, A.; Alessandrini, A.; Piscopo, R.; Mazzarello, G.; Belvisi, V.; Caramma, I.; Chiodera, A.; Castelli, P.; Moroni, M.; Puoti, M.; Galli, M.; Lazzarin, A.; Rizzardini, G.; Ridolfo, A. L.; Piolini, R.; Rusconi, S.; Balotta, C.; Castagna, A.; Marchetti, G.; Tincati, C.; Cicconi, P.; Moioli, M. C.; Cinque, P.; Gianotti, N.; Salpietro, S.; Galli, L.; Carenzi, L.; Iardino, R.; Tavelli, A.; Mussini, C.; Guaraldi, G.; Marcotullio, S.; Puzzolante, C.; Lapadula, G.; Abrescia, N.; Chirianni, A.; Borgia, G.; Maddaloni, A.; Gargiulo, M.; Gentile, I.; Orlando, R.; Baldelli, F.; Francisci, D.; Parruti, G.; Ursini, T.; Magnani, G.; Ursitti, Ma.; Cauda, R.; Antinori, A.; Andreoni, M.; Vullo, V.; Ceccherini-Silberstein, F.; Cingolani, A.; Girardi, E.; D'Avino, A.; Fanti, I.; Gallo, L.; Ippolito, G.; Perno, C. F.; Lichtner, M.; Capobianchi, M. R.; Nicastri, E.; Acinapura, R.; Ammassari, A.; Capozzi, M.; Tebano, G.; Lorenzini, P.; Von Schloesser, F.; Zaccarelli, M.; Viviani, F.; Sasset, L.; Mura, M. S.; De Luca, A.; Rossetti, B.; Caramello, P.; Di Perri, G.; Orofino, G.; Sciandra, M.; Bassetti, M.; Londero, A.; Pellizzer, G.; Manfrin, V.
abstract

Whilst renal dysfunction, especially mild impairment (60 die;ve (Icona) Foundation Study collected between January 2000 and February 2014 with at least two creatinine values available. eGFR (CKD-epi) and renal dysfunction defined using a priori cut-offs of 60 (severely impaired) and 90 ml/min/1.73m2 (mildly impaired). Characteristics of patients were described after stratification in these groups and compared using chi-square test (categorical variables) or Kruskal Wallis test comparing median values. Follow-up accrued from baseline up to the date of the CCVD or AIDS related events or death or last available visit. Kaplan Meier curves were used to estimate the cumulative probability of occurrence of the events over time. Adjusted analysis was performed using a proportional hazards Cox regression model. We included 7,385 patients, observed for a median follow-up of 43 months (interquartile range [IQR]: 21-93 months). Over this time, 130 cerebro-cardiovascular events (including 11 deaths due to CCVD) and 311 AIDS-related events (including 45 deaths) were observed. The rate of CCVD events among patients with eGFR &gt;90, 60-89, &lt;60 ml/min, was 2.91 (95% CI 2.30-3.67), 4.63 (95% CI 3.51-6.11) and 11.9 (95% CI 6.19-22.85) per 1,000 PYFU respectively, with an unadjusted hazard ratio (HR) of 4.14 (95%CI 2.07-8.29) for patients with eGFR &lt;60 ml/min and 1.58 (95%CI 1.10-2.27) for eGFR 60-89 compared to those with eGFR ≥90. Of note, these estimates are adjusted for traditional cardiovascular risk factors (e.g. smoking, diabetes, hypertension, dyslipidemia). Incidence of AIDS-related events was 9.51 (95%CI 8.35-10.83), 6.04 (95%CI 4.74-7.71) and 25.0 (95% CI 15.96-39.22) per 1,000 PYFU, among patients with eGFR &gt;90, 60-89, &lt;60 ml/min, respectively, with an unadjusted HR of 2.49 (95%CI 1.56-3.97) for patients with eGFR &lt;60 ml/min and 0.68 (95%CI 0.52-0.90) for eGFR 60-89. The risk of AIDS events was significantly lower in mild renal dysfunction group even after adjustment for HIV-related characteristics. Our data confirm that impaired renal function is an important risk marker for CCVD events in the HIV-population; importantly, even those with mild renal impairment (90&lt;60)&gt;

2015 - Full Viral Suppression, Low-Level Viremia, and Quantifiable Plasma HIV-RNA at the End of Pregnancy in HIV-Infected Women on Antiretroviral Treatment [Articolo su rivista]
Baroncelli, Silvia; Pirillo, Maria F.; Tamburrini, Enrica; Guaraldi, Giovanni; Pinnetti, Carmela; Degli Antoni, Anna; Galluzzo, Clementina M.; Stentarelli, Chiara; Amici, Roberta; Floridia, Marco
abstract

There is limited information on full viral suppression and low-level HIV-RNA viremia in HIV-infected women at the end of pregnancy. We investigated HIV-RNA levels close to delivery in women on antiretroviral treatment in order to define rates of complete suppression, low-level viremia, and quantifiable HIV-RNA, exploring as potential determinants some clinical and viroimmunological variables. Plasma samples from a national study in Italy, collected between 2003 and 2012, were used. According to plasma HIV-RNA levels, three groups were defined: full suppression (target not detected), low-level viremia (target detected but <37 copies/ml), and quantifiable HIV-RNA (≥37 copies/ml). Multivariable logistic regression was used to define determinants of full viral suppression and of quantifiable HIV-RNA. Among 107 women evaluated at a median gestational age of 35 weeks, 90 (84.1%) had HIV-RNA <37 copies/ml. Most of them (59/90, 65.6%) had full suppression, with the remaining (31/90, 34.4%) showing low-level viremia (median: 11.9 copies/ml; IQR 7.4-16.3). Among the 17 women with quantifiable viral load, median HIV-RNA was 109 copies/ml (IQR 46-251), with only one case showing resistance (mutation M184V; rate: 9.1%). In multivariable analyses, women with higher baseline HIV-RNA levels and with hepatitis C virus (HCV) coinfection were significantly more likely to have quantifiable HIV-RNA in late pregnancy. Full viral suppression was significantly more likely with nonnucleoside reverse transcriptase inhibitor (NNRTI)-based regimens and significantly less likely with higher HIV-RNA in early pregnancy. No cases of HIV transmission occurred. In conclusion, HIV-infected pregnant women showed a high rate of viral suppression and a low resistance rate before delivery. In most cases no target HIV-RNA was detected in plasma, suggesting a low risk of subsequent virological rebound and development of resistance. Women with high levels of HIV-RNA in early pregnancy and those who have concomitant HCV infection should be considered at higher risk of having quantifiable HIV-RNA at the end of pregnancy.

2015 - Good prenatal detection rate of major birth defects in HIV-infected pregnant women in Italy [Articolo su rivista]
Floridia, M.; Mastroiacovo, P.; Ravizza, M.; Todros, T.; Chiado Fiorio Tin, M.; Marconi, A. M.; Cetin, I.; Maruotti, G. M.; Liuzzi, G.; Pinnetti, C.; Degli Antoni, A.; Spinillo, A.; Guerra, B.; Tamburrini, E.; Floridia, M.; Ravizza, M.; Tamburrini, E.; Ravizza, M.; Tamburrini, E.; Mori, F.; Ortolani, P.; dalle Nogare, E. R.; Di Lorenzo, F.; Sterrantino, G.; Meli, M.; Polemi, S.; Nocentini, J.; Baldini, M.; Montorzi, G.; Mazzetti, M.; Rogasi, P.; Borchi, B.; Vichi, F.; Del Pin, B.; Pinter, E.; Anzalone, E.; Marocco, R.; Mastroianni, C.; Mercurio, V. S.; Carocci, A.; Grilli, E.; Maccabruni, A.; Zaramella, M.; Mariani, B.; Natalini Raponi, G.; Guaraldi, G.; Nardini, G.; Stentarelli, C.; Beghetto, B.; Degli Antoni, A. M.; Molinari, A.; Crisalli, M. P.; Donisi, A.; Piepoli, M.; Cerri, V.; Zuccotti, G.; Giacomet, V.; Coletto, S.; Di Nello, F.; Madia, C.; Placido, G.; Vivarelli, A.; Castelli, P.; Savalli, F.; Portelli, V.; Sabbatini, F.; Francisci, D.; Bernini, L.; Grossi, P.; Rizzi, L.; Alberico, S.; Maso, G.; Airoud, M.; Soppelsa, G.; Meloni, A.; Dedoni, M.; Cuboni, C.; Ortu, F.; Piano, P.; Citernesi, A.; Bordoni Vicini, I.; Luzi, K.; Spinillo, A.; Roccio, M.; Vimercati, A.; Miccolis, A.; De Gennaro, A.; Guerra, B.; Cervi, F.; Puccetti, C.; Margarito, E.; Contoli, M.; Capretti, M. G.; Marsico, C.; Faldella, G.; Sansone, M.; Martinelli, P.; Agangi, A.; Capone, A.; Maruotti, G. M.; Tibaldi, C.; Trentini, L.; Todros, T.; Masuelli, G.; Frisina, V.; Cetin, I.; Brambilla, T.; Savasi, V.; Personeni, C.; Giaquinto, C.; Fiscon, M.; Rinaldi, R.; Rubino, E.; Bucceri, A.; Matrone, R.; Scaravelli, G.; Fundaro, C.; Genovese, O.; Cafforio, C.; Pinnetti, C.; Liuzzi, G.; Tozzi, V.; Massetti, P.; Casadei, A. M.; Cavaliere, A. F.; Finelli, V.; Cellini, M.; Castelli Gattinara, G.; Dalzero, S.; Sacchi, V.; Ierardi, M.; Polizzi, C.; Mattei, A.; Pirillo, M. F.; Amici, R.; Galluzzo, C. M.; Donnini, S.; Baroncelli, S.; Floridia, M.; Villani, P.; Cusato, M.; Cerioli, A.; De Martino, M.; Mastroiacovo, P.; Parazzini, F.; Tamburrini, E.; Vella, S.; Martinelli, P.; Ravizza, M.
abstract

What's already known about this topic? Exposure to antiretroviral treatment in pregnancy does not seem to increase the risk of birth defects, but there is no information on the rate of prenatal detection of such defects. What does this study adds? We provide for the first time, in a national case series, information about prenatal detection rate in women with HIV (51.6% for any major defect, 66.7% for chromosomal abnormalities, and 85% for severe structural defects).

2015 - Health transitions in HIV-seropositive individulas undergoing NRTI-based and NRTI-sparing treatment strategies. [Abstract in Rivista]
Zona, Stefano; Malagoli, Andrea; Stentarelli, Chiara; Mussini, Cristina; Guaraldi, Giovanni
abstract

NRTI-sparing strategies are often prescribed to reduce the impact of drug toxicities on age related co-morbidities, particularly relevant in frail individuals. The objective of this study was to assess the impact of NRTI-sparing strategies on health transitions in HIV-infected patients with well-controlled HIV infection using a multi-item frailty index.

2015 - HIV patients exhibit similar rates of emphysema progression observed in older HIV-uninfected patients with higher cumulative smoke exposure. [Abstract in Rivista]
Leung, J; Malagoli, Andrea; Santoro, Antonella; Besutti, Giulia; Ligabue, Guido; Dai, D; Mayo, J; Lam, S; Sin, D; Man, S; Guaraldi, Giovanni
abstract

HIV patients face the burden of chronic obstructive pulmonary disease (COPD). How quickly COPD phenotypes such as emphysema progress, what risk factors are associated with COPD progression in an HIV-infected population, and whether this risk of progression is in excess compared to HIV-uninfected patients are unknown.

2015 - HIV patients exhibit similar rates of emphysema progression observed in older HIV-uninfected patients with higher cumulative smoke exposure. [Abstract in Rivista]
Malagoli, Andrea; Santoro, Antonella; Besutti, Giulia; Ligabue, Guido; Guaraldi, Giovanni
abstract

HIV patients face the burden of chronic obstructive pulmonary disease (COPD). How quickly COPD phenotypes such as emphysema progress, what risk factors are associated with COPD progression in an HIV-infected population, and whether this risk of progression is in excess compared to HIV-uninfected patients are unknown.

2015 - HIV patients undergoing second generation antipsychotics show high cardiovascular disease burden [Abstract in Rivista]
Ferrara, M; Malagoli, Andrea; Garlassi, Sara; Stentarelli, Chiara; Zona, Stefano; Carli, Federica; Menozzi, Marianna; Santoro, Antonella; Raggi, P; Starace, F; Mussini, Cristina; Guaraldi, Giovanni
abstract

Cardiovascular disease is highly prevalent in HIV-positive patients and can be explored with coronary artery calcium score as a biomarker of preclinical coronary disease. Antiretroviral drugs and concomitant treatment including second generation anti-psychotics may contribute to metabolic derangement with potential impact on traditional cardiovascular risk factors associated with the metabolic syndrome phenotype. The objective of the study was to assess the impact of second generation anti-psychotics on subclinical cardiovascular disease in HIV positive patients.

2015 - How do frailty mediate pathway leading to disability [Abstract in Rivista]
Malagoli, Andrea; Garlassi, Sara; Stentarelli, Chiara; Carli, Federica; Menozzi, Marianna; Santoro, Antonella; Beghetto, Barbara; Nardini, Giulia; Mussini, Cristina; Guaraldi, Giovanni
abstract

HIV infection increases the risk of multimorbidity (MM) and disability but factors influencing the association between the two are still poorly understood. We hypothesized that frailty mediate pathway leading to disability.

2015 - IAPAC guidelines for optimizing the HIV care continuum for adults and adolescents [Articolo su rivista]
Bekker, L. -G.; Montaner, J.; Ramos, C.; Sherer, R.; Celletti, F.; Cutler, B.; Dabis, F.; Granich, R.; Greenberg, A.; Goldenberg, S.; Hull, M.; Kerr, T.; Kurth, A.; Mayer, K.; Metsch, L.; Mugo, N. R.; Munderi, P.; Nachega, J.; Nosyk, B.; Saavedra, J.; Wolters, T.; Young, B.; Zuniga, J. M.; Agins, B.; Amico, K. R.; Begovac, J.; Beyrer, C.; Cahn, P.; Cairns, G.; Cohen, M.; Deering, K.; Del Rio, C.; Diaz, R. S.; Dombrowski, J. C.; Doshi, R.; El-Sadr, W.; Futterman, D.; Geretti, A. M.; Guaraldi, G.; Halloran, J.; Gordon, C. M.; Kahana, S.; Lama, J.; Lima, V. D.; Linsk, N.; Monforte, A. D.; Nelson, M.; Negussie, E.; Phanuphak, P.; Scott, J.; Shaffer, D.; Shannon, K.; Spaulding, A.; Valerio, C.; Wu, Z.; Zakowicz, A.; Zorrilla, C.
abstract

Background: An estimated 50% of people living with HIV (PLHIV) globally are unaware of their status. Among those who know their HIV status, many do not receive antiretroviral therapy (ART) in a timely manner, fail to remain engaged in care, or do not achieve sustained viral suppression. Barriers across the HIV care continuum prevent PLHIV from achieving the therapeutic and preventive effects of ART. Methods: A systematic literature search was conducted, and 6132 articles, including randomized controlled trials, observational studies with or without comparators, cross-sectional studies, and descriptive documents, met the inclusion criteria. Of these, 1047 articles were used to generate 36 recommendations to optimize the HIV care continuum for adults and adolescents. Recommendations: Recommendations are provided for interventions to optimize the HIV care environment; increase HIV testing and linkage to care, treatment coverage, retention in care, and viral suppression; and monitor the HIV care continuum.

2015 - Incidence and factors associated with the risk of sexually transmitted diseases in HIV-infected people seen for care in Italy: data from the Icona Foundation cohort [Articolo su rivista]
Cingolani, A.; Zona, Stefano; Girardi, E.; Cozzi Lepri, A.; Monno, L.; Quiros Roldan, E.; Guaraldi, Giovanni; Antinori, A.; D'Arminio Monforte, A.; Marcotullio, S.
abstract

The aims of this study were to identify temporal trends in the incidence of sexually transmitted diseases (STDs) in a cohort of HIV-infected people and to evaluate factors associated with the risk of a new STD diagnosis.

2015 - Is "Option B+" Also Being Adopted in Pregnant Women in High-Income Countries? Temporal Trends From a National Study in Italy. [Articolo su rivista]
Floridia, M; Guaraldi, Giovanni; Ravizza, M; Tibaldi, C; Pinnetti, C; Maccabruni, A; Molinari, A; Liuzzi, G; Alberico, S; Meloni, A; Rizzi, L; Dalzero, S; Tamburrini, E.
abstract

non disponibile

2015 - LIVER RESECTION FOR HCC IN HIV-INFECTED PATIENTS: A SINGLE CENTER EXPERIENCE [Articolo su rivista]
D'Amico, G; Tarantino, G; Ballarin, R; Serra, V; Pecchi, A R; Guaraldi, G; Di Benedetto, F
abstract

HIV-infected patients now live longer and often have complications of liver disease, especially with hepatitis B or C virus co-infection. Hepatocellular carcinoma (HCC) is an increasing cause of mortality in HIV positive and negative individuals. There is a lack of consensus regarding the clinical presentation, treatment options, and outcome in HIV-infected patients with HCC. Unfortunately, HCC is frequently diagnosed at an advanced stage, and mortality continues to be very high. Earlier diagnosis, which may allow potentially curative therapy, is necessary. Liver resection is considered the most potentially curative treatment for HCC patients when liver transplantation is not an option or is not immediately accessible. The aim of this article was to describe our liver resection strategy, describing our experience, for HCC in HIV infected patients.

2015 - Low testosterone is associated with poor health status in men with human immunodeficiency virus infection: a retrospective study [Articolo su rivista]
Rochira, Vincenzo; Diazzi, Chiara; Santi, Daniele; Brigante, Giulia; Ansaloni, Anna; Decaroli, Maria Chiara; De Vincentis, Sara; Stentarelli, Chiara; Zona, Stefano; Guaraldi, Giovanni
abstract

Men with human immunodeficiency virus (HIV) infection are often hypogonadal and develop several HIV-associated non-acquired immunodeficiency syndrome (AIDS) (HANA) conditions that impair overall health status. No studies explored the relationship between health status and serum testosterone (T) in HIV-infected men. This study aims to investigate the association between total serum T and HANA, multimorbidity, and frailty in a large cohort of 1359 HIV-infected men and to explore the relationship between patients' overall health status and serum T. Among biochemical and hormonal measurement performed the main are serum total T, free triiodothyronine (fT3), and luteinizing hormone. Other outcome measurements include anthropometry, assessment of comorbidities and disabilities, overall health status defined as the number of HANA and by the 38-item multimorbidity frailty index, anthropometry, and bone mineral density. The cumulative relative risk of comorbidities is increased in HIV-infected men with hypogonadism (p < 0.001) and hypogonadism is associated with several comorbidities. The prevalence of hypogonadism increases progressively with the increase of the number of comorbidities. Frailty index is inversely related to serum total T (age-adjusted r = 0.298, r(2) = 0.089, p < 0.0001). Serum fT3 levels are significantly lower in hypogonadal than eugonadal men (p = 0.022). This suggests that low serum T could be considered a sensitive marker of frailty and poor health status and that the latter might induce hypogonadism. The more HIV-infected men are frail the more they are hypogonadal. This suggests that hypogonadism might be a naturally occurring condition in unhealthy HIV-infected men and raises concern about the safety of T treatment. In conclusion, low serum T is associated with multimorbidity, HANA, and frailty in HIV-infected men and this association seems to be bidirectional. Given the wide attitude to offer T treatment to HIV-infected men, caution is needed when prescribing T to HIV-infected male patients, especially if the patient is unhealthy or frail.

2015 - Lung and Heart Diseases Are Better Predicted by Pack-Years than by Smoking Status or Duration of Smoking Cessation in HIV Patients [Articolo su rivista]
Guaraldi, Giovanni; Raggi, Paolo; Gomes, André; Zona, Stefano; Marchi, Enrico; Santoro, Antonella; Besutti, Giulia; Scaglioni, Riccardo; Ligabue, Guido; Leipsic, Jonathon; Man, Paul; Sin, Don
abstract

BACKGROUND: The objective of this study was to assess the relationship of pack-years smoking and time since smoking cessation with risk of lung and heart disease. METHODS: We investigated the history of lung and heart disease in 903 HIV-infected patients who had undergone thoracic computed tomography (CT) imaging stratified by smoking history. Multimorbidity lung and heart disease (MLHD) was defined as the presence of ≥ 2 clinical or subclinical lung abnormalities and at least one heart abnormality. RESULTS: Among 903 patients, 23.7% had never smoked, 28.7% were former smokers and 47.6% were current smokers. Spirometry indicated chronic obstructive pulmonary disease in 11.4% of patients and MLHD was present in 53.6%. Age, male sex, greater pack-years smoking history and smoking cessation less than 5 years earlier vs. more than 10 years earlier (OR 2.59, 95% CI 1.27-5.29, p = 0.009) were independently associated with CT detected subclinical lung and heart disease. Pack-years smoking history was more strongly associated with MLHD than smoking status (p<0.001). CONCLUSIONS: MLHD is common even among HIV-infected patients who never smoked and pack- years smoking history is a stronger predictor than current smoking status of MLHD. A detailed pack-years smoking history should be routinely obtained and smoking cessation strategies implemented

2015 - Number of Cardiometabolic disorders is associated with degree of frailty among people aging with HIV. [Abstract in Rivista]
Brothers, Td; Wallace, Lmk; Malagoli, Andrea; Rossi, Rosario; Manicardi, Marcella; Santoro, Antonella; Theou, O; Kirkland, S; Rockwood, K; Guaraldi, Giovanni
abstract

Inflammatory cardiometabolic disorders become more common and can accumulate with age. Frailty also worsens with age and is associated with pro-inflammatory states. We sought to assess the burden of cardiometabolic disorders in a large ongoing HIV-positive cohort study, the relationship between cardiometaolic disorders and frailty, and whether they independently contribute to mortality.

2015 - Prognostic Value of the Fibrosis-4 Index in Human Immunodeficiency Virus Type-1 Infected Patients Initiating Antiretroviral Therapy with or without Hepatitis C Virus [Articolo su rivista]
Mussini, Cristina; Lorenzini, Patrizia; Puoti, Massimo; Lichtner, Miriam; Lapadula, Giuseppe; Di Giambenedetto, Simona; Antinori, Andrea; Madeddu, Giordano; Cozzi-Lepri, Alessandro; D'Arminio Monforte, Antonella; De Luca, Andrea; Moroni, M.; Andreoni, M.; Angarano, G.; Antinori, A.; D'Arminio Monforte, A.; Castelli, F.; Cauda, R.; Di Perri, G.; Galli, M.; Iardino, R.; Ippolito, G.; Lazzarin, A.; Perno, C. F.; Von Schloesser, F.; Viale, P.; D'Arminio Monforte, A.; Antinori, A.; Castagna, A.; Ceccherini-Silberstein, F.; Cozzi-Lepri, A.; Girardi, E.; Lo Caputo, S.; Mussini, C.; Puoti, M.; Andreoni, M.; Ammassari, A.; Antinori, A.; Balotta, C.; Bandera, A.; Bonfanti, P.; Bonora, S.; Borderi, M.; Calcagno, A.; Calza, L.; Capobianchi, M. R.; Castagna, A.; Ceccherini-Silberstein, F.; Cingolani, A.; Cinque, P.; Cozzi-Lepri, A.; D'Arminio Monforte, A.; De Luca, A.; Di Biagio, A.; Girardi, E.; Gianotti, N.; Gori, A.; Guaraldi, G.; Lapadula, G.; Lichtner, M.; Lo Caputo, S.; Madeddu, G.; Maggiolo, F.; Marchetti, G.; Marcotullio, S.; Monno, L.; Mussini, C.; Nozza, S.; Puoti, M.; Quiros Roldan, E.; Rossotti, R.; Rusconi, S.; Santoro, M. M.; Saracino, A.; Zaccarelli, M.; Cozzi-Lepri, A.; Fanti, I.; Galli, L.; Lorenzini, P.; Rodano, A.; Shanyinde, M.; Tavelli, A.
abstract

Objective: To evaluate the Fibrosis (FIB)-4 index as a predictor of major liver-related events (LRE) and liver-related death (LRD) in human immunodeficiency virus (HIV) type-1 patients initiating combination antiretroviral therapy (cART). Design: Retrospective analysis of a prospective cohort study. Setting: Italian HIV care centers participating to the ICONA Foundation cohort. Participants: Treatment-naive patients enrolled in ICONA were selected who: initiated cART, had hepatitis C virus (HCV) serology results, were HBsAg negative, had an available FIB-4 index at cART start and during follow up. Methods: Cox regression models were used to determine the association of FIB4 with the risk of major LRE (gastrointestinal bleeding, ascites, hepatic encephalopathy, hepato-renal syndrome or hepatocellular carcinoma) or LRD. Results: Three-thousand four-hundred seventy-five patients were enrolled: 73.3% were males, 27.2% HCV seropositive. At baseline (time of cART initiation) their median age was 39 years, had a median CD4+ T cell count of 260 cells/uL, and median HIV RNA 4.9 log copies/ mL, 65.9% had a FIB-4 &lt; 1.45, 26.4% 1.45-3.25 and 7.7% &gt; 3.25. Over a follow up of 18,662 person-years, 41 events were observed: 25 major LRE and 16 LRD (incidence rate, IR, 2.2 per 1,000 PYFU [95% confidence interval, CI 1.6-3.0]). IR was higher in HCV seropositives as compared to negatives (5.9 vs 0.5 per 1,000 PYFU). Higher baseline FIB-4 category as compared to &lt; 1.45 (FIB-4 1.45-3.25: HR 3.55, 95% CI 1.09-11.58; FIB-4 &gt; 3.25: HR 4.25, 1.21-14.92) and time-updated FIB-4 (FIB-4 1.45-3.25: HR 3.40, 1.02-11.40; FIB- 4&gt; 3.25: HR 21.24, 6.75-66.84) were independently predictive of major LRE/LRD, after adjusting for HIV- and HCV-related variables, alcohol consumption and type of cART. Conclusions: The FIB-4 index at cART initiation, and its modification over time are risk factors for major LRE or LRD, independently of infection with HCV and could be used to monitor patients on cART.

2015 - Recommendations for evaluation and management of bone disease in HIV [Articolo su rivista]
Brown, Todd T.; Hoy, Jennifer; Borderi, Marco; Guaraldi, Giovanni; Renjifo, Boris; Vescini, Fabio; Yin, Michael T.; Powderly, William G.
abstract

Thirty-four human immunodeficiency virus (HIV) specialists from 16 countries contributed to this project, whose primary aim was to provide guidance on the screening, diagnosis, and monitoring of bone disease in HIV-infected patients. Four clinically important questions in bone disease management were identified, and recommendations, based on literature review and expert opinion, were agreed upon. Risk of fragility fracture should be assessed primarily using the Fracture Risk Assessment Tool (FRAX), without dual-energy X-ray absorptiometry (DXA), in all HIV-infected men aged 40-49 years and HIV-infected premenopausal women aged ≥40 years. DXA should be performed in men aged ≥50 years, postmenopausal women, patients with a history of fragility fracture, patients receiving chronic glucocorticoid treatment, and patients at high risk of falls. In resource-limited settings, FRAX without bone mineral density can be substituted for DXA. Guidelines for antiretroviral therapy should be followed; adjustment should avoid tenofovir disoproxil fumarate or boosted protease inhibitors in at-risk patients. Dietary and lifestyle management strategies for high-risk patients should be employed and antiosteoporosis treatment initiated.

2015 - Renal hyperfiltration and outcome in HIV-infected subjects. [Abstract in Rivista]
Bellasi, A; Ascione, E; Malagoli, Andrea; Zona, Stefano; Rubbiani, E; Carli, Federica; Stentarelli, Chiara; Mussini, Cristina; Cappelli, Gianni; Guaraldi, Giovanni
abstract

Evidence from the general population suggests that renal hyperfiltration portends poor prognosis in the general population. No data in HIV-infected subjects is available. Hence, we investigated prevalence, associations with traditional and HIV-related risk factors as well as the prognostic significance of renal hyperfiltration in a large cohort of HIV-infected subjects.

2015 - Serum gonadotropins secretion is not reduced with advancing age in HIV-infected females: results of a case–control study in menopausal women. [Abstract in Rivista]
Diazzi, Chiara; Brigante, Giulia; Guaraldi, Giovanni; Simoni, Manuela; Rochira, Vincenzo
abstract

Introduction HIV infection treated with highly active antiretroviral therapy (HAART) seems to be associated with hypogonadism in men. Less is known in HIV-infected women gonadal status. The aim of this study is to investigate gonadal function, in menopausal HIV-infected women compared sex- and age-matched healthy subjects (HS). Methods We retrospectively compared 188 HIV-infected women with 192 HS selected reviewing record charts and laboratory database respectively. We considered only women older than 50 years and we grouped them according to their age (50–54; 55–59; and O60 years). Basal serum LH, FSH, estradiol, and testosterone were measured. The FSH cut-off of 40 UI/l for establishing menopausal status. Results The percentage of subjects with FSH levels O40 UI/l was higher in HIV-infected women (67.5%) than in healthy controls (59.4%). This difference was found also in the younger subgroup (38% vs 27%). FSH serum levels in HIV-infected women (54.08G31.47 mUI/ml) did not differ (PZ0.27) from HS (50.87G 31 mUI/ml). Accordingly, no significant differences were found in LH, estradiol, and testosterone levels. Conclusions Menopause seems to occur at a younger age than HS in HIV-infected women. Moreover, differently from what was documented in HIV-infected male counterpart, HIV-infected women seem to not develop hypogonadotropic hypogonadism, but have a tendency to higher serum FSH at a younger age (!54 years) suggesting premature hypergonadotropic hypogonadism. With this in view menopause may be considered an element of the process of premature aging associated with HIV infection and its comorbidities.

2015 - Should we screen for NAFLD/NASH in HIV patients? [Abstract in Rivista]
Guaraldi, Giovanni; Malagoli, Andrea; Stentarelli, Chiara; Manicardi, Marcella; Zona, Stefano; Carli, Federica; Menozzi, Marianna; Santoro, Antonella; Franceschini, Erica; Mussini, Cristina
abstract

NAFLD is expected to be the most prevalent liver disease in the post-HCV era. The clinical impact of NAFLD and the benefit of screening with biochemical based algorithms is a metter of concern.

2015 - Two methods of measuring frailty among people aging with HIV [Abstract in Rivista]
Guaraldi, Giovanni; Torelli, R; Malagoli, Andrea; Brothers, Tl; Wallace, L; Garlassi, Sara; Santoro, Antonella; Stentarelli, Chiara; Carli, Federica; Sartini, S; Theou, O; Kirkland, S; Zona, Stefano; Rockwood, K.
abstract

The two most common methods of assessing frailty are via the frailty phenotype and the frailty index. We assessed and compared their cross-sectional characteristics in the same sample of people aging with HIV in northern Italy.

2014 - ARE ARBS THE PREFERRED AGENTS TO TREAT HYPERTENSION IN PATIENTS WITH HIVNEPHROPATHY WITH ALBUMINURIA [Capitolo/Saggio]
B., Di Iorio; A., Bellasi; Guaraldi, Giovanni
abstract

Numerous signs of renal dysfunction such as proteinuria, crystalluria and microhematuria as well as a variety of other renal syndromes may characterize the course of HIV infection and lead to renal failure. It is estimated that approximately 1% to 2% of patients starting dialysis suffer from HIV-associated renal disease. HIV-associated nephropathy (HIVAN) occurs in about 10% of HIV-infected subjects with a distinct predilection for Blacks and Hispanic individuals. This nephropathy is characterized by glomerular basement membrane thickening, wrinkling and folding, segmental or global collapse of the glomerular tufts, increase in the Bowman space, and podocytes abnormalities. Large podocytes filled with protein droplets often accumulate in layers around the collapsed areas forming the pseudocrescents. Tubular atrophy, interstitial inflammation and different degree of fibrosis are generally associated with the glomerular damage. Until antiretroviral therapy (ART) became available, HIVAN was characterized by a rapid renal function decline and progression to end-stage renal disease. Aside from the HIV direct injury to the nephron, numerous experimental observations lend support to the notion that Angiotensin II contributes to podocytes damage and treatment with angiotensin-converting enzyme inhibitors (ACE-Is) as well as angiotensin receptor

2014 - Atazanavir and lopinavir profile in pregnant women with HIV: tolerability, activity and pregnancy outcomes in an observational national study [Articolo su rivista]
M., Floridia; M., Ravizza; G., Masuelli; V., Giacomet; P., Martinelli; A., Degli Antoni; A., Spinillo; M., Fiscon; D., Francisci; G., Liuzzi; C., Pinnetti; A. M., Marconi; E., Tamburrini; M., Floridia; M., Ravizza; E., Tamburrini; M., Ravizza; E., Tamburrini; F., Mori; P., Ortolani; E. R., dalle Nogare; F., Di Lorenzo; G., Sterrantino; M., Meli; S., Polemi; J., Nocentini; M., Baldini; G., Montorzi; M., Mazzetti; P., Rogasi; B., Borchi; F., Vichi; B., Del Pin; E., Pinter; E., Anzalone; R., Marocco; C., Mastroianni; V. S., Mercurio; A., Carocci; E., Grilli; A., Maccabruni; M., Zaramella; B., Mariani; G., Natalini Raponi; Guaraldi, Giovanni; Nardini, Giulia; Stentarelli, Chiara; Beghetto, Barbara; A. M., Degli Antoni; A., Molinari; M. P., Crisalli; A., Donisi; M., Piepoli; V., Cerri; G., Zuccotti; V., Giacomet; V., Fabiano; G., Placido; A., Vivarelli; P., Castelli; F., Savalli; V., Portelli; F., Sabbatini; D., Francisci; L., Bernini; P., Grossi; L., Rizzi; S., Alberico; G., Maso; M., Airoud; G., Soppelsa; A., Meloni; M., Dedoni; C., Cuboni; F., Ortu; P., Piano; A., Citernesi; I., Bordoni Vicini; K., Luzi; A., Spinillo; M., Roccio; A., Vimercati; A., Miccolis; E., Bassi; B., Guerra; F., Cervi; C., Puccetti; P., Murano; M., Contoli; M. G., Capretti; C., Marsico; G., Faldella; M., Sansone; P., Martinelli; A., Agangi; C., Tibaldi; L., Trentini; T., Todros; G., Masuelli; V., Frisina; I., Cetin; T., Brambilla; V., Savasi; C., Personeni; C., Giaquinto; M., Fiscon; R., Rinaldi; E., Rubino; A., Bucceri; R., Matrone; G., Scaravelli; C., Fundaro; O., Genovese; C., Cafforio; C., Pinnetti; G., Liuzzi; V., Tozzi; P., Massetti; A. M., Casadei; A. F., Cavaliere; V., Finelli; M., Cellini; G., Castelli Gattinara; A. M., Marconi; S., Dalzero; V., Sacchi; A., De Pirro; C., Polizzi; A., Mattei; M. F., Pirillo; R., Amici; C. M., Galluzzo; S., Donnini; S., Baroncelli; M., Floridia; M., Regazzi; P., Villani; M., Cusato; A., Cerioli; M., De Martino; P., Mastroiacovo; M., Moroni; F., Parazzini; E., Tamburrini; S., Vella; P., Martinelli; M., Ravizza
abstract

CKGROUND: Atazanavir and lopinavir represent the main HIV protease inhibitors recommended in pregnancy, but comparative data in pregnant women are limited. METHODS: Women from a national observational study, exposed in pregnancy to either atazanavir or lopinavir, were compared for glucose and lipid profiles, liver function tests, CD4 count, HIV RNA and main pregnancy outcomes. Statistical methods included univariate and multivariable analyses. RESULTS: The study population included 428 pregnancies (lopinavir, 322; atazanavir, 106). The lopinavir group was characterized by higher rates of HIV diagnosis in pregnancy and treatment indication for maternal health, lower CD4 counts, higher HIV RNA levels, less frequent antiretroviral treatment at conception and shorter duration of drug exposure during pregnancy. No differences in pregnancy outcomes, glucose metabolism and weight gain were observed. The two groups also showed in a multivariable analysis similar odds for detectable HIV RNA in the third trimester (adjusted OR 0.85, 95% CI 0.35-2.10, P = 0.730). Total lipid levels were significantly higher in the lopinavir group (median values in the third trimester 239 versus 221 mg/dL for total cholesterol and 226 versus 181 mg/dL for triglycerides; P &lt; 0.001 for both comparisons) and bilirubin levels were significantly higher in the atazanavir group (1.53 versus 0.46 mg/dL, P &lt; 0.001). CONCLUSIONS: In this observational study atazanavir and lopinavir showed similar safety and activity in pregnancy, with no differences in the main pregnancy outcomes. Atazanavir use was associated with a better lipid profile and with higher bilirubin levels. Overall, the study findings confirm that these two HIV protease inhibitors represent equally valid alternative options.

2014 - Atazanavir/ritonavir monotherapy as maintenance strategy in HIV-1 treated subjects with viral suppression: 96-week analysis results of the MODAT study [Abstract in Rivista]
Spagnuolo, Vincenzo; Galli, Laura; Bigoloni, Alba; Nozza, Silvia; Monforte, Antonella d'Arminio; Antinori, Andrea; Di Biagio, Antonio; Rusconi, Stefano; Guaraldi, Giovanni; Di Giambenedetto, Simona; Lazzarin, Adriano; Castagna, Antonella
abstract

The 48-week interim analysis of the MODAT study showed that confirmed virologic failure (CVF) was more frequent in patients simplifying to ATV/r monotherapy compared to maintaining ATV/r-based triple therapy. The DSMB recommended stopping study enrollment but continuing follow-up of enrolled patients. We present the 96-week efficacy analysis.

2014 - Atazanavir/ritonavir monotherapy as maintenance strategy in HIV-1 treated subjects with viral suppression: 96-week analysis results of the MODAT study [Articolo su rivista]
Spagnuolo, Vincenzo; Galli, Laura; Bigoloni, Alba; Nozza, Silvia; Monforte, Antonella d'Arminio; Antinori, Andrea; Di Biagio, Antonio; Rusconi, Stefano; Guaraldi, Giovanni; Di Giambenedetto, Simona; Lazzarin, Adriano; Castagna, Antonella
abstract

The 48-week interim analysis of the MODAT study showed that confirmed virologic failure (CVF) was more frequent in patients simplifying to ATV/r monotherapy compared to maintaining ATV/r-based triple therapy. The DSMB recommended stopping study enrollment but continuing follow-up of enrolled patients. We present the 96-week efficacy analysis.

2014 - Burden of subclinical heart and lung disease detected on thoracic CT scans of HIV patients on HAART [Abstract in Rivista]
Zona, Stefano; Santoro, Antonella; Besutti, Giulia; Ligabue, Guido; Mussini, Cristina; Raggi, Paolo; Leipsic, Jonathon; Sin, Don D; Guaraldi, Giovanni
abstract

The aim was to determine the prevalence of lung and heart abnormalities on thoracic CT scans in HIV-infected patients who were treated with antiretroviral therapy (ART).

2014 - Clinical and epidemiological features of HIV/AIDS infection among migrants at first access to healthcare services as compared to Italian patients in Italy: a retrospective multicentre study, 2000-2010. [Articolo su rivista]
G., Sulis; I., El Hamad; M., Fabiani; S., Rusconi; F., Maggiolo; Guaraldi, Giovanni; G., Bozzi; C., Bernardini; M., Lichtner; Stentarelli, Chiara; L., Carenzi; D., Francisci; A., Saracino; F., Castelli; The HIV/Migrants Study, Group
abstract

Migrants account for approximately 8.7 % of the resident population in Italy. The immigration status deeply influences access to prevention and care, thus contributing to increase the burden of HIV/AIDS among such a fragile category. The aim of this study was to investigate socio-demographic and baseline clinical and immunological features of HIV-infected migrants, as compared to Italians. We retrospectively analysed data for all the 1,611 HIV-infected migrant patients and a random sample of 4,230 HIV-infected Italian patients aged 18 or older who first accessed nine Italian clinical centres in 2000-2010 and were followed up at least 1 year. Differences in baseline characteristics between migrants and Italians were evaluated in univariate analysis, while factors associated with late presentation were evaluated in multivariate analysis using logistic regression models. The baseline profile differs between the HIV-infected migrant and Italian patients, substantially reflecting what reported by current statistics in terms of gender, age, risk category as well as clinical features. Late presenters were more frequent among migrants as compared to Italians (53.0 vs 45.8 %; adjusted odds ratio [(AOR) = 1.55, 95 % confidence interval (CI) 1.34-1.78]. Other factors associated with late presentation included increasing age, as well as undocumented legal status among foreign-born subjects (AOR = 1.41, 95 % CI 0.97-2.04), though of borderline significance. Late presentation still represents a relevant problem despite the advances in the management of HIV infection. More efforts are needed to allow early diagnosis and access to care among the most vulnerable, such as undocumented foreign-born subjects in a country where migration flows are on the rise.

2014 - Development of a definition for Rapid Progression (RP) of renal function in HIV-positive persons: The D:A:D study [Articolo su rivista]
Kamara, D. A.; Ryom, L.; Ross, M.; Kirk, O.; Reiss, P.; Morlat, P.; Moranne, O.; Fux, C. A.; Mocroft, A.; Sabin, C.; Lundgren, J. D.; Smith, C. J.; Powderly, B.; Shortman, N.; Moecklinghoff, C.; Reilly, G.; Franquet, X.; Ryom, L.; Sabin, C. A.; Kamara, D.; Smith, C.; Phillips, A.; Mocroft, A.; Tverland, J.; Mansfeld, M.; Nielsen, J.; Raben, D.; Lundgren, J. D.; Salbol Brandt, R.; Rickenbach, M.; Fanti, I.; Krum, E.; Hillebregt, M.; Geffard, S.; Sundstrom, A.; Delforge, M.; Fontas, E.; Torres, F.; Mcmanus, H.; Wright, S.; Kjaer, J.; Sjol, A.; Meidahl, P.; Helweg-Larsen, J.; Schmidt Iversen, J.; Ryom, L.; Mocroft, A.; Kirk, O.; Reiss, P.; Ross, M.; Fux, C. A.; Morlat, P.; Moranne, O.; Kesselring, A. M.; Kamara, D. A.; Smith, C.; Lundgren, J. D.; Smith, C.; Ryom, L.; Phillips, A.; Weber, R.; Morlat, P.; Pradier, C.; Reiss, P.; Friis-Moller, N.; Kowalska, J.; Lundgren, J. D.; Sabin, C.; Law, M.; D'Arminio Monforte, A.; Dabis, F.; Bruyand, M.; Reiss, P.; Smith, C.; Kamara, D. A.; Bower, M.; Fatkenheuer, G.; Donald, A.; Grulich, A.; Ryom, L.; Lundgren, J. D.; Reiss, P.; Zaheri, S.; Hillebregt, M.; Gras, L.; Prins, J. M.; Kuijpers, T. W.; Scherpbier, H. J.; Van Der Meer, J. T. M.; Wit, F. W. M. N.; Godfried, M. H.; Reiss, P.; Van Der Poll, T.; Nellen, F. J. B.; Lange, J. M. A.; Geerlings, S. E.; Van Vugt, M.; Pajkrt, D.; Bos, J. C.; Van Der Valk, M.; Grijsen, M. L.; Wiersinga, W. J.; Goorhuis, A.; Hovius, J. W. R.; Lowe, S.; Oude Lashof, A.; Posthouwer, D.; Pronk, M. J. H.; Ammerlaan, H. S. M.; Van Der Ende, M. E.; De Vries-Sluijs, T. E. M. S.; Schurink, C. A. M.; Nouwen, J. L.; Verbon, A.; Rijnders, B. J. A.; Van Gorp, E. C. M.; Van Der Feltz, M.; Driessen, G. J. A.; Van Rossum, A. M. C.; Branger, J.; Schippers, E. F.; Van Nieuwkoop, C.; Van Elzakker, E. P.; Groeneveld, P. H. P.; Bouwhuis, J. W.; Soetekouw, R.; Ten Kate, R. W.; Kroon, F. P.; Van Dissel, J. T.; Arend, S. M.; De Boer, M. G. J.; Jolink, H.; Ter Vollaard, H. J. M.; Bauer, M. P.; Den Hollander, J. G.; Pogany, K.; Van Twillert, G.; Kortmann, W.; Cohen Stuart, J. W. T.; Diederen, B. M. W.; Leyten, E. M. S.; Gelinck, L. B. S.; Kootstra, G. J.; Delsing, C. E.; Brinkman, K.; Blok, W. L.; Frissen, P. H. J.; Schouten, W. E. M.; Van Den Berk, G. E. L.; Van Kasteren, M. E. E.; Brouwer, A. E.; Veenstra, J.; Lettinga, K. D.; Mulder, J. W.; Vrouenraets, S. M. E.; Lauw, F. N.; Van Eeden, A.; Verhagen, D. W. M.; Sprenger, H. G.; Doedens, R.; Scholvinck, E. H.; Van Assen, S.; Bierman, W. F. W.; Koopmans, P. P.; Keuter, M.; Van Der Ven, A. J. A. M.; Ter Hofstede, H. J. M.; Dofferhoff, A. S. M.; Warris, A.; Van Crevel, R.; Hoepelman, A. I. M.; Mudrikova, T.; Schneider, M. M. E.; Ellerbroek, P. M.; Oosterheert, J. J.; Arends, J. E.; Wassenberg, M. W. M.; Barth, R. E.; Van Agtmael, M. A.; Perenboom, R. M.; Claessen, F. A. P.; Bomers, M.; Peters, E. J. G.; Geelen, S. P. M.; Wolfs, T. F. W.; Bont, L. J.; Richter, C.; Van Der Berg, J. P.; Gisolf, E. H.; Van Den Berge, M.; Stegeman, A.; Van Vonderen, M. G. A.; Van Houte, D. P. F.; Weijer, S.; El Moussaoui, R.; Winkel, C.; Muskiet, F.; Durand, ; Voigt, R.; Dabis, F.; Bruyand, M.; Chene, G.; Dabis, F.; Lawson-Ayayi, S.; Thiebaut, R.; Bonnal, F.; Bonnet, F.; Bernard, N.; Caunegre, L.; Cazanave, C.; Ceccaldi, J.; Chambon, D.; Chossat, I.; Dauchy, F. A.; De Witte, S.; Dupon, M.; Duffau, P.; Dutronc, H.; Farbos, S.; Gaborieau, V.; Gemain, M. C.; Gerard, Y.; Greib, C.; Hessamfar, M.; Lacoste, D.; Lataste, P.; Lafarie, S.; Lazaro, E.; Malvy, D.; Meraud, J. P.; Mercie, P.; Monlun, E.; Morlat, P.; Neau, D.; Ochoa, A.; Pellegrin, J. L.; Pistone, T.; Ragnaud, J. M.; Receveur, M. C.; Tchamgoue, S.; Vandenhende, M. A.; Viallard, J. F.; Moreau, J. F.; Pellegrin, I.; Fleury, H.; Lafon, M. E.; Masquelier, B.; Trimoulet, P.; Breilh, D.; Haramburu, F.; Miremont-Salame, G.; Blaizeau, M. J.; Decoin, M.; Delaune, J.; Delveaux, S.; D'Ivernois, C.; Hanapier, C.; Leleux, O.; Uwamaliya-Nziyumvira, B.; Sicard, X.; Geffard, S.; Palmer, G.; Touchard, D.; Bonnet, F.; Dupon
abstract

Background: No consensus exists on how to define abnormally rapid deterioration in renal function (Rapid Progression, RP). We developed an operational definition of RP in HIV-positive persons with baseline estimated glomerular filtration rate (eGFR) &gt;90 ml/min/1.73 m2 (using Cockcroft Gault) in the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study from 2004 to 2011. Methods: Two definitions were evaluated; RP definition A: An average eGFR decline (slope) =5 ml/min/1.73 m2/year over four years of follow-up with =3 eGFR measurements/year, last eGFR &lt;90 ml/min/1.73 m2 and an absolute decline =5 ml/min/1.73 m2/year in two consecutive years. RP definition B: An absolute annual decline =5 ml/min/1.73 m2/year in each year and last eGFR &lt;90 ml/min/1.73 m2. Sensitivity analyses were performed considering two and three years' follow-up. The percentage with and without RP who went on to subsequently develop incident chronic kidney disease (CKD; 2 consecutive eGFRs &lt;60 ml/min/1.73 m2 and 3 months apart) was calculated. Results: 22,603 individuals had baseline eGFR =90 ml/min/1.73 m2. 108/3655 (3.0%) individuals with =4 years' follow-up and =3 measurements/year experienced RP under definition A; similar proportions were observed when considering follow-up periods of three (n=195/6375; 3.1%) and two years (n=355/10756; 3.3%). In contrast under RP definition B, greater proportions experienced RP when considering two years (n=476/10756; 4.4%) instead of three (n=48/6375; 0.8%) or four (n=15/3655; 0.4%) years' follow-up. For RP definition A, 13 (12%) individuals who experienced RP progressed to CKD, and only (21) 0.6% of those without RP progressed to CKD (sensitivity 38.2% and specificity 97.4%); whereas for RP definition B, fewer RP individuals progressed to CKD. Conclusions: Our results suggest using three years' follow-up and at least two eGFR measurements per year is most appropriate for a RP definition, as it allows inclusion of a reasonable number of individuals and is associated with the known risk factors. The definition does not necessarily identify all those that progress to incident CKD, however, it can be used alongside other renal measurements to early identify and assess those at risk of developing CKD. Future analyses will use this definition to identify other risk factors for RP, including the role of antiretrovirals.

2014 - Evolution of HIV-1 tropism at quasispecies level after 5 years of combination antiretroviral therapy in patients always suppressed or experiencing episodes of virological failure [Articolo su rivista]
Rozera, G.; Abbate, I.; Giombini, E.; Castagna, A.; de Luca, A.; Ceccherini-Silberstein, F.; Lepri, A. C.; Cassola, G.; Torti, C.; d'Arminio Monforte, A.; Ippolito, G.; Capobianchi, M. R.; Moroni, M.; Andreoni, M.; Angarano, G.; Antinori, A.; Castelli, F.; Cauda, R.; Di Perri, G.; Galli, M.; Iardino, R.; Lazzarin, A.; Perno, C. F.; von Schloesser, F.; Viale, P.; Cozzi-Lepri, A.; Girardi, E.; Lo Caputo, S.; Mussini, C.; Puoti, M.; Ammassari, A.; Balotta, C.; Bonfanti, P.; Bonora, S.; Borderi, M.; Cingolani, A.; Cinque, P.; di Biagio, A.; Gianotti, N.; Gori, A.; Guaraldi, G.; Lapadula, G.; Lichtner, M.; Madeddu, G.; Maggiolo, F.; Marchetti, G.; Marcotullio, S.; Monno, L.; Quiros Roldan, E.; Rusconi, S.; Cicconi, P.; Fanti, I.; Formenti, T.; Galli, L.; Lorenzini, P.; Carletti, F.; Carrara, S.; Castrogiovanni, A.; di Caro, A.; Petrone, F.; Prota, G.; Quartu, S.; Giacometti, A.; Costantini, A.; Mazzoccato, S.; Santoro, C.; Suardi, C.; Vanino, E.; Verucchi, G.; Minardi, C.; Quirino, T.; Abeli, C.; Manconi, P. E.; Piano, P.; Vecchiet, J.; Falasca, K.; Sighinolfi, L.; Segala, D.; Mazzotta, F.; Viscoli, C.; Alessandrini, A.; Piscopo, R.; Mazzarello, G.; Mastroianni, C.; Belvisi, V.; Caramma, I.; Chiodera, A.; Castelli, A. P.; Rizzardini, G.; Ridolfo, A. L.; Piolini, R.; Salpietro, S.; Carenzi, L.; Moioli, M. C.; Tincati, C.; Puzzolante, C.; Abrescia, N.; Chirianni, A.; Guida, M. G.; Gargiulo, M.; Baldelli, F.; Francisci, D.; Parruti, G.; Ursini, T.; Magnani, G.; Ursitti, M. A.; Vullo, V.; d'Avino, A.; Gallo, L.; Nicastri, E.; Acinapura, R.; Capozzi, M.; Libertone, R.; Tebano, G.; Cattelan, A.; Sasset, L.; Mura, M. S.; Rossetti, B.; Caramello, P.; Orofino, G. C.; Sciandra, M.; Bassetti, M.; Londero, A.; Pellizzer, G.; Manfrin, V.
abstract

Objectives: Tropism evolution of HIV-1 quasispecies was analysed by ultra-deep pyrosequencing (UDPS) in patients on first-line combination antiretroviral therapy (cART) always suppressed or experiencing virological failure episodes. Methods: Among ICONA patients, two groups of 20 patients on cART for ≥5 years, matched for baseline viraemia and therapy duration, were analysed [Group I, patients always suppressed; and Group II, patients experiencing episode(s) of virological failure]. Viral tropism was assessed by V3 UDPS on plasma RNA before therapy (T0) and on peripheral blood mononuclear cell proviral DNA before-after therapy (T0-T1), using geno2pheno false positive rate (FPR) (threshold for X4: 5.75). For each sample, quasispecies tropism was assigned according to X4 variant frequency: R5, &lt; 0.3% X4; minority X4, 0.3%-19.9% X4; and X4, ≥20% X4. An R5-X4 switch was defined as a change from R5/minority X4 in plasma/proviral genomes at T0 to X4 in provirus at T1. Results: At baseline, mean FPR and %X4 of viral RNA were positively correlated with those of proviral DNA. After therapy, proviral DNA load significantly decreased in Group I; mean FPR of proviral quasispecies significantly decreased and %X4 increased in Group II. An R5-X4 switch was observed in five patients (two in Group I and three in Group II), all harbouring minority X4 variants at T0. Conclusions: UDPS analysis reveals that the tropism switch is not an 'on-off' phenomenon, but may result from a profound re-shaping of viral quasispecies, even under suppressive cART. However, episodes of virological failure seem to prevent reduction of proviral DNA and to accelerate viral evolution, as suggested by decreased FPR and increased %X4 at T1 in Group II patients.

2014 - Frailty in People Aging With Human Immunodeficiency Virus (HIV) Infection. [Articolo su rivista]
Brothers, T. D.; S., Kirkland; Guaraldi, Giovanni; J., Falutz; O., Theou; Johnston, B. L.; K., Rockwood
abstract

The increasing life spans of people infected with human immunodeficiency virus (HIV) reflect enormous treatment successes and present new challenges related to aging. Even with suppression of viral loads and immune reconstitution, HIV-positive individuals exhibit excess vulnerability to multiple health problems that are not AIDS-defining. With the accumulation of multiple health problems, it is likely that many people aging with treated HIV infection may be identified as frail. Studies of frailty in people with HIV are currently limited but suggest that frailty might be feasible and useful as an integrative marker of multisystem vulnerability, for organizing care and for comprehensively measuring the impact of illness and treatment on overall health status. This review explains how frailty has been conceptualized and measured in the general population, critically reviews emerging data on frailty in people with HIV infection, and explores how the concept of frailty might inform HIV research and care.

2014 - Funzione gonadica e sessuale in uomini giovani/adulti con infezione da Human Immunodeficiency Virus (HIV) [Abstract in Atti di Convegno]
Santi, Daniele; Brigante, Giulia; C., Diazzi; S., De Vincentis; Zona, Stefano; Guaraldi, Giovanni; Simoni, Manuela; Rochira, Vincenzo
abstract

This study investigates male sexual function in men with HIV infection according with their gonadal status and circulating androgens

2014 - Gender differences in GH response to GHRH+ARG in lipodystrophic patients with HIV: a key role for body fat distribution [Articolo su rivista]
Brigante, Giulia; Diazzi, Chiara; Ansaloni, Anna; Zirilli, Lucia; Orlando, Gabriella; Guaraldi, Giovanni; Rochira, Vincenzo
abstract

OBJECTIVE: Gender influence on GH secretion in human immunodeficiency virus (HIV)-infected patients is poorly known. DESIGN AND METHODS: To determine the effect of gender, we compared GH response to GH-releasing hormone plus arginine (GHRH+Arg), and body composition in 103 men and 97 women with HIV and lipodystrophy. The main outcomes were IGF1, basal GH, GH peak and area under the curve (AUC) after GHRH+Arg, body composition, visceral adipose tissue (VAT), and subcutaneous adipose tissue (SAT). RESULTS: Men had lower GH peak and AUC than women (P&lt;0.001). Of the study population, 21% of women and 37% of men had biochemical GH deficiency (GHD; GH peak &lt;7.5 μg/l). VAT-to-SAT ratio was higher in men than in women with GHD (P&lt;0.05). Unlike women, VAT, SAT, and trunk fat were greater in men with GHD than in men without GHD. IGF1 was significantly lower in women with GHD than in women without GHD, but not in men. At univariate analysis, BMI, trunk fat mass, VAT, and total adipose tissue were associated with GH peak and AUC in both sexes (P&lt;0.05). BMI was the most significant predictive factor of GH peak, and AUC at multiregression analysis. Overall, abdominal fat had a less pronounced effect on GH in females than in males. CONCLUSIONS: These data demonstrate that GH response to GHRH+Arg is significantly lower in HIV-infected males than females, resulting in a higher percentage of GHD in men. Adipose tissue distribution more than fat mass per se seems to account for GH gender differences and for the alteration of GH-IGF1 status in these patients.

2014 - GH deficiency in HIV-infected patients compared to hypoopituitary patients [Abstract in Rivista]
Diazzi, Chiara; Brigante, Giulia; G., Ferrannini; Guaraldi, Giovanni; Ansaloni, Anna; Simoni, Manuela; Rochira, Vincenzo
abstract

The difference between HIV-infected patients with growth hormone deficiency (GHD) and GHD patients with hypopituitarism is in higher values go GH peak after GHRH+Arginine and IGF-1 in men with HIV.

2014 - GH deficiency in HIV-infected patients compared to hypopituitary patients [Abstract in Rivista]
Brigante, Giulia; Diazzi, Chiara; G., Ferrannini; S., De Vincentis; Guaraldi, Giovanni; Ansaloni, Anna; Simoni, Manuela; Rochira, Vincenzo
abstract

Gh peak after GHR+Arginine and IGF-1 are lower in HIV-infected patients with biochemical growth hormone deficiency than in patients with hypopituitarism and GHD.

2014 - Gonadal and sexual function in young/middle aged human immunodeficiency virus (HIV)-infected men [Abstract in Rivista]
Santi, Daniele; Brigante, Giulia; Diazzi, Chiara; S., De Vincentis; Zona, Stefano; Guaraldi, Giovanni; Simoni, Manuela; Rochira, Vincenzo
abstract

The study investigated male sexual function in men with HIV infection according with their gonadal status.

2014 - Hypogonadism in the HIV-infected man [Articolo su rivista]
Rochira, Vincenzo; Guaraldi, Giovanni
abstract

Androgen deficiency occurs frequently in men with human immunodeficiency virus (HIV) infection. Antiretroviral treatments had reduced the prevalence of male hypogonadism. The pathogenesis of testosterone (T) deficiency in HIV is multifactorial. Several mechanisms have been proposed; among them, drugs, fat redistribution, and a poor health status could explain the mechanism leading to gonadotropins inhibition and hypogonadotropic hypogonadism. The diagnosis of hypogonadism in HIV-infected men should be made based on clinical symptoms and a specific workup including T measurement. The interpretation of the results of biochemical testing is more difficult in men with HIV due to several confounding factors. T treatment should be offered to HIV-infected men with documented clinical hypogonadism and symptoms, especially if they are losing lean mass.

2014 - I pazienti con infezione da HIV hanno un reale deficit di GH (GHD) ? Confronto tra pazienti HIV positivi con documentato GHD biochimico e pazienti ipopituitarici HIV negativi con GHD [Abstract in Atti di Convegno]
Brigante, Giulia; Diazzi, Chiara; G., Ferrannini; Guaraldi, Giovanni; Ansaloni, Anna; Simoni, Manuela; Rochira, Vincenzo
abstract

The response to GHRH+Arginine is higher in HIV-infected patients with GHD when compared to patients with GHD and hypopituitarism

2014 - Impact of Antiretroviral Medications on Fasting Lipid Parameters [Articolo su rivista]
Guaraldi, Giovanni; Santoro, Antonella; Stentarelli, Chiara; K., Luzi
abstract

It is widely accepted that metabolic disease in human immunodeficiency virus (HIV) develops at the intersection of traditional risk factors and HIV-specific contributors, but in observational studies it is difficult to dissect the contribution of the two. This review describes the metabolic impact of antiretroviral medications recommended in the first-line treatment in HIV-infected naive patients. At a clinical level, coronary heart disease screening and management will continue to be of paramount importance in the long-term management of HIV-positive patients on antiretroviral therapy.

2014 - Inhibition of the Renin-Angiotensin System in HIV nephropathy [Articolo su rivista]
Guaraldi, Giovanni; Dolci, Giovanni; Bellasi, A; Di Iorio, B.
abstract

It is estimated that 1-2 % of patients starting dialysis suffers from kidney disease associated with HIV infection. HIV-associated nephropathy ( HIVAN ) develops in about 10% of people living with HIV , with different preference for Blacks and Hispanics . Since the beginning of large-scale use of antiretroviral therapy (ART), the HIVAN has been characterized by a rapid decline in renal function , with progression to ESRD ( End - Stage Renal Disease ). Aside from HIV direct damage to the nephron, numerous experimental observations support the argument that the agiotensina II contributes to the podocytes damage. Treatment with ACE - inhibitors (ACE - Is) , as well as the one with angiotensin receptor blockers ( ARBs), may attenuate the decline in renal function in HIVAN . However, clinical data on the effects of these antihypertensive agents in HIV-infected individuals are still scarce and doubts have yet to be adequately addressed. In the following, we analyze the studies that have investigated the use of ACE -Is and ARBs in the treatment of hypertension and albuminuria in patients with HIVAN.

2014 - Intact parathyroid hormone levels are associated with increased carotid intima media thickness in HIV infected patients [Articolo su rivista]
Antonio, Bellasi; Paolo, Raggi; Rossi, Rosario; Rochira, Vincenzo; Stentarelli, Chiara; Zona, Stefano; Antonella, Lattanzi; Carli, Federica; Mussini, Cristina; Guaraldi, Giovanni
abstract

Aim. Preliminary evidence suggests that intact parathyroid hormone (iPTH) and bone mineral abnormalities may contribute to the development of vascular disease and are associated with reduced survival in the general population. Whether iPTH is associated with subclinical atherosclerosis in HIV-infected individuals has not been elucidated. Methods. Cross-sectional study of 470 consecutive HIV-infected patients in whom we measured carotid intima-media thickness (cIMT), and collected demographical, clinical and laboratory data. High-cIMT was defined as a mean IMT above the 75th percentile for the study cohort. Parametric, non-parametric tests and logistic regression analyses were used to compare patients' characteristics between low- and high-cIMT and to test the association between high-cIMT and log-transformed iPTH. Results. Of the 470 patients, 130 had high-cIMT. High-cIMT subjects were older and more likely to be male and have a history of cardiovascular disease. Glucose, lipid and iPTH levels were lower among low-cIMT subjects (p < 0.05). Unadjusted and multivariable adjusted analyses demonstrated an independent association between high-cIMT and iPTH (fully adjusted OR: 1.74; 95%CI: 1.08–2.79; p = 0.021). Bootstrap and sensitivity analyses confirmed these findings. Conclusions. Elevated iPTH was associated with subclinical atherosclerosis in HIV-infected subjects. Of note this association was statistically significant even for iPTH values within the range of normality. The existence of a causal relationship between iPTH and atherosclerosis needs to be fully explored in future investigations.

2014 - Life Expectancy in the Immune Recovery Era [Articolo su rivista]
Guaraldi, Giovanni; Cossarizza, Andrea; C., Franceschi; A., Roverato; E., Vaccher; G., Tambussi; E., Garlassi; Menozzi, Marianna; Mussini, Cristina; A., DʼArminio Monforte
abstract

INTRODUCTION: National cohort and intercohort studies have been set to describe the differences of life expectancy (LE) of HIV-infected individuals. OBJECTIVE: The aim of this study was to assess the impact of immune recovery (IR) on LE of patients with HIV undergoing combination antiretroviral therapy. METHODS: In this retrospective observational study, outcome measure was LE of patients with HIV compared with LE of northern Italian population. Group categorizations were as follows: patients with no immune recovery (nIR), patients with IR, patients who are immune maintained, and pre-highly active antiretroviral therapy (HAART) and post-HAART. Abridged life tables were constructed from age-specific mortality rates (per 1000 person years) to estimate LE from the age of 20-55 years. RESULTS: A total of 9671 patients, 71% men, were included. After 2005, we assisted to a rapid increase in the overall rate of patients attaining IR in the community coupled with a progressive decrease of AIDS death, but not of non-AIDS deaths. In a 40-year-old patient, LE was 38.10 years [standard error (SE) = 2.60], 30.08 years (SE = 0.98), and 22.9 (SE = 0.69) in the IR, post-HAART group and nIR, respectively, compared with 41.38 years of the general Italian population. An approximately 5-year gap in LE was observed in IR patients. DISCUSSION: We describe IR at a "community" level, related to calendar year and apparent 10 years after HAART introduction. HAART community IR is significantly influencing LE and is associated with the changing clinical picture of HIV disease. An increasing gradient of LE exists between nIR, post-HAART, and IR groups, with the latter, above the age of 40 years only, reaching LE of general population.

2014 - Longitudinal analysis of HIV-1 coreceptor tropism by single and triplicate HIV-1 RNA and DNA sequencing in patients undergoing successful first-line antiretroviral therapy [Articolo su rivista]
G., Meini; B., Rossetti; C., Bianco; F., Ceccherini Silberstein; S., Di Giambenedetto; L., Sighinolfi; L., Monno; A., Castagna; G., Rozera; A., D'Arminio Monforte; M., Zazzi; A., De Luca; M., Moroni; G., Angarano; A., Antinori; O., Armignacco; A., d'Arminio Monforte; F., Castelli; R., Cauda; G., Di Perri; M., Galli; R., Iardino; G., Ippolito; A., Lazzarin; C. F., Perno; F., von Schloesser; P., Viale; A., Castagna; F., Ceccherini Silberstein; A., Cozzi Lepri; E., Girardi; S., Lo Caputo; Mussini, Cristina; M., Puoti; M., Andreoni; A., Ammassari; C., Balotta; P., Bonfanti; S., Bonora; M., Borderi; M. R., Capobianchi; A., Cingolani; P., Cinque; A., De Luca; A., Di Biagio; N., Gianotti; A., Gori; Guaraldi, Giovanni; G., Lapadula; M., Lichtner; G., Madeddu; F., Maggiolo; G., Marchetti; S., Marcotullio; L., Monno; E., Quiros Roldan; S., Rusconi; P., Cicconi; I., Fanti; T., Formenti; L., Galli; P., Lorenzini; A., Giacometti; A., Costantini; C., Santoro; C., Suardi; E., Vanino; G., Verucchi; C., Minardi; T., Quirino; C., Abeli; P. E., Manconi; P., Piano; J., Vecchiet; K., Falasca; L., Sighinolfi; D., Segala; F., Mazzotta; G., Cassola; G., Viscoli; A., Alessandrini; R., Piscopo; G., Mazzarello; C., Mastroianni; V., Belvisi; I., Caramma; A. P., Castelli; G., Rizzardini; A. L., Ridolfo; R., Piolini; S., Salpietro; L., Carenzi; M. C., Moioli; C., Puzzolante; N., Abrescia; A., Chirianni; M. G., Guida; M., Gargiulo; F., Baldelli; D., Francisci; G., Parruti; T., Ursini; G., Magnani; M. A., Ursitti; V., Vullo; A., D'Avino; L., Gallo; E., Nicastri; R., Acinapura; M., Capozzi; R., Libertone; G., Tebano; A., Cattelan; M. S., Mura; P., Caramello; G. C., Orofino; M., Sciandra; G., Pellizzer; V., Manfrin
abstract

OBJECTIVES: Maraviroc has been shown to be effective in patients harbouring CCR5-tropic HIV-1. While this CCR5 antagonist has initially been used in salvage therapy, its excellent safety profile makes it ideal for antiretroviral treatment simplification strategies in patients with suppressed plasma viraemia. The aim of this study was to compare HIV-1 tropism as detected in baseline plasma RNA and peripheral blood mononuclear cell (PBMC) DNA prior to first-line therapy and to analyse tropism evolution while on successful treatment. METHODS: HIV-1 tropism was determined using triplicate genotypic testing combined with geno2pheno[coreceptor] analysis at a 10% false positive rate in 42 patients. Paired pre-treatment plasma RNA and PBMC DNA and two subsequent PBMC DNA samples (the first obtained after reaching undetectable plasma HIV-1 RNA and the second after at least 2 years of suppression of plasma viraemia) were evaluated. RESULTS: Coreceptor tropism was completely concordant in paired pre-treatment RNA and DNA, with 26.2% of HIV-1 sequences predicted to be non-CCR5-tropic. During follow-up, coreceptor tropism switches were detected in 4 (9.5%) patients without any preferential direction. Although false positive rate discrepancies within triplicates were common, the rate of discordance of coreceptor tropism assignment among triplicate results in this mostly CCR5-tropic dataset was only 2.1%, questioning the added value of triplicate testing compared with single testing. CONCLUSIONS: HIV-1 coreceptor tropism changes during virologically successful first-line treatment are infrequent. HIV-1 DNA analysis may thus support the choice of a CCR5 antagonist in treatment switch strategies; however, maraviroc treatment outcome data are required to confirm this option.

2014 - Male sexual dysfunction and HIV-a clinical perspective [Articolo su rivista]
Santi, Daniele; Brigante, Giulia; Zona, Stefano; Guaraldi, Giovanni; Rochira, Vincenzo
abstract

Sexual dysfunction in men with HIV is often overlooked by clinicians owing to many factors, including the taboo of sexuality. The improved life expectancy of patients with HIV requires physicians to consider their general wellbeing and sexual health with a renewed interest. However, data on sexual dysfunction in those with HIV are scarce. Erectile dysfunction (ED) is the most common sexual dysfunction in men, with a prevalence of ∼30-50% and is frequent even in men <40 years of age. HIV infection itself is the strongest predictor of ED, and many factors related to the infection-fear of virus transmission, changes in body image, HIV-related comorbidities, infection stigma, obligatory condom use-all impair erectile function. The diagnosis and treatment of sexual dysfunction is based on a multidisciplinary approach, which involves specialists in both infectious diseases and sexual medicine. Particular attention should be paid to the promotion of safer sex in these patients. This Review, describes the issues surrounding sexual dysfunction in men with HIV and aims to provide clinical advice for the physician treating these patients.

2014 - Metabolic alterations in HIV-infected pregnant women: moving to metabolic tailoring of antiretroviral drugs. [Articolo su rivista]
Guaraldi, Giovanni; Stentarelli, Chiara; A. D., Da Silva; K., Luzi; Neri, Isabella; M., Cellini; E., Petrella; E., Garlassi; Menozzi, Marianna; Facchinetti, Fabio; Mussini, Cristina
abstract

The most striking effect of increased survival and improved quality of life in HIV-infected women undergoing antiretroviral therapy is the feasibility of motherhood-desire satisfaction. However, such advantages are often associated with drug-related metabolic toxicities, particularly relevant in the pregnancy context. Recent guidelines provide recommendations and trends for the use of antiretroviral therapy in pregnant women, but current literature falls short of providing specific insights on the need for metabolic monitoring and treatment in HIV-infected pregnant women. In this review we provide specific insight into the state-of-the-art of: detection, evaluation, and management of metabolic alterations in this special population. Pregnancy is in fact a metabolic transition process, potentially associated with specific diseases in the mother, in the newborn, and in the adulthood of the child. We will not simply discuss antiretroviral therapy metabolic toxicities, but rather their interaction with the physiological metabolic changes occurring during pregnancy. Close monitoring is needed to diagnose metabolic alterations that can lead to adverse outcomes in the mother, in the newborn, and potentially in adulthood. Lifestyle interventions and an appropriate metabolic tailoring of antiretroviral therapy drugs need to be considered in the prevention and treatment of metabolic alteration during pregnancy.

2014 - Morbidity in Older HIV-Infected Patients: Impact of Long-Term Antiretroviral Use. [Articolo su rivista]
Guaraldi, Giovanni; M., Prakash; C., Moecklinghoff; Stellbrink, H. J.
abstract

The introduction of HAART has represented a major advance in the care of people with HIV. By markedly increasing life expectancy, HAART has significantly changed the pattern of HIV infection in developed countries, the "graying" of the HIV-infected population being a powerful testament to its success. However, this has presented physicians with new challenges relating to the care of older patients with HIV, many of whom exhibit a "frailty syndrome" associated with increased comorbidity and chronic low-grade inflammation in a process which has recently been termed "inflammaging". This paper reviews the pattern of morbidity seen in older HIV-infected patients and examines the effects, both beneficial and deleterious, of antiretroviral therapy. The efficacy and tolerability of antiretroviral therapy is of particular importance in older patients, given the likelihood that increased frailty may magnify the consequences both of suboptimal viral suppression and of toxicity, and in view of the complications that may arise from the presence of comorbidities and resultant polypharmacy. The challenge is to maximize antiviral efficacy and minimize toxicity, while taking into account the often complex web of comorbidities that may be present in these patients. This challenge is being met through the refinement of existing antiretroviral therapy regimens, the development of new agents, and a growing focus on a more holistic approach to care, which acknowledges the importance of the overall "health picture" and of good communication and cooperation between treating physicians and patients.

2014 - Multimorbidity and functional status assessment [Articolo su rivista]
Guaraldi, Giovanni; A. R., Silva; Stentarelli, Chiara
abstract

Purpose of review: This review conceptualizes multimorbidity and functional status impairment in people living with HIV and their implication in clinical and research fields. Recent findings: Multimorbidity is an increasing age-related condition whose prevalence is higher in HIV-infected patients compared with the general population. It portrays the contemporary clinical complexity of HIV care. Whether multimorbidity describes an accelerated or accentuated aging process is the matter of discussion, although some HIV variables depicting immune activation and chronic inflammation are associated with multimorbidity. Multimorbidity coupled with functional status impairment are determinants of a frailty phenotype and in the frailty research setting, multimorbidity can be explored as an endpoint for clinical studies. Summary: The success of highly active antiretroviral therapy has significantly changed the clinical pattern of HIV infection, with the 'greying' of the HIV-infected population testament to its success. This has provided new challenges relating to the care of older patients, particularly with regard to the management of multimorbidity functional status impairment.

2014 - Rate, Predictors, and Consequences of Late Antenatal Booking in a National Cohort Study of Pregnant Women With HIV in Italy [Articolo su rivista]
M., Floridia; C., Pinnetti; M., Ravizza; V., Frisina; I., Cetin; M., Fiscon; M., Sansone; A., Degli Antoni; Guaraldi, Giovanni; A., Vimercati; B., Guerra; G., Placido; S., Dalzero; E., Tamburrini
abstract

To evaluate the prevalence and consequences of late antenatal booking (13 or more weeks gestation) in a national observational study of pregnant women with HIV. Methods: The clinical and demographic characteristics associated with late booking were evaluated in univariate analyses using the Mann-Whitney U test for quantitative data and the chi-square test for categorical data. The associations that were found were re-evaluated in multivariable logistic regression models. Main outcomes were preterm delivery, low birthweight, nonelective cesarean section, birth defects, undetectable (<50 copies/mL) HIV plasma viral load at third trimester, delivery complications, and gender-adjusted and gestational age-adjusted Z scores for birthweight. Results: Rate of late booking among 1,643 pregnancies was 32.9%. This condition was associated with younger age, African provenance, diagnosis of HIV during pregnancy, and less antiretroviral exposure. Undetectable HIV RNA at third trimester and preterm delivery were significantly more prevalent with earlier booking (67.1% vs 46.3%, P < .001, and 23.2% vs 17.6, P = .010, respectively), whereas complications of delivery were more common with late booking (8.2% vs 5.0%, P = .013). Multivariable analyses confirmed an independent role of late booking in predicting detectable HIV RNA at third trimester (adjusted odds ratio [AOR], 1.7; 95% CI, 1.3-2.3; P < .001) and delivery complications (AOR, 1.8; 95% CI, 1.2-2.8; P = .005). Conclusions: Late antenatal booking was associated with detectable HIV RNA in late pregnancy and with complications of delivery. Measures should be taken to ensure an earlier entry into antenatal care, particularly for African women, and to facilitate access to counselling and antenatal services. These measures can significantly improve pregnancy management and reduce morbidity and complications in pregnant women with HIV.

2014 - Recommendations for the use of hepatitis C virus protease inhibitors for the treatment of chronic hepatitis C in HIV-infected persons. A position paper of the Italian Association for the Study of Infectious and Tropical Disease [Articolo su rivista]
Armignacco, Orlando; Andreoni, Massimo; Sagnelli, Evangelista; Puoti, Massimo; Bruno, Raffaele; Gaeta, Giovanni Battista; Perno, Carlo F; Santantonio, Teresa A; Bonfanti, Paolo; Bonora, Stefano; Borderi, Marco; Castagna, Antonella; d'Arminio Monforte, Antonella; De Luca, Andrea; Grossi, Paolo; Guaraldi, Giovanni; Maggiolo, Franco; Mussini, Cristina; Sagnelli, Caterina; Tavio, Marcello; Torti, Carlo; Uberti Foppa, Caterina; Andreoni, Massimo; Angarano, Gioacchino; Antinori, Andrea; Armignacco, Orlando; Carosi, Giampiero; Chirianni, Antonio; Di Perri, Giovanni; Galli, Massimo; Lazzarin, Adriano; Rizzardini, Giuliano; Sagnelli, Evangelista; Taliani, Gloria
abstract

The efficacy data obtained with boceprevir and telaprevir for persons with hepatitis C virus (HCV) genotype 1 infection raise the question of whether HCV protease inhibitors should be used in human immunodeficiency virus (HIV)/HCV co-infected persons. The Italian Association for the Study of Infectious and Tropical Diseases has made these recommendations to provide the rationale and practical indications for the use of triple anti-HCV therapy in persons living with HIV (PLWHIV). A Writing Committee of experts indicated by the President of the Association and a Consulting Committee con- tributed to the document. The final draft was submitted to the evaluation of external experts and the text modified according to their suggestions and comments. Treatment of HCV co-infection should be considered for all HCV RNA positive PLWHIV. Response-guided therapy with pegylated interferon and ribavirin is the standard treatment of PLWHIV with infection by HCV genotype 2, 3, 4, 5 and 6. Boceprevir and telaprevir should be used to treat HCV genotype 1 infection in HIV/HCV co-infected patients for 48 weeks on an individual basis, with close monitoring of their efficacy and tolerability with concur- rent antiretroviral therapy, taking into account potential drug-drug interactions. The decision to treat a patient or to wait for better treatment options, or to discontinue treatment should be made on an individual basis taking into account pre-treatment variables and the on-treatment HCV RNA kinetics.

2014 - Relationship Between Health-Related Quality of Life Measures and High HIV Viral Load in HIV-Infected Triple-Class-Experienced Patients [Articolo su rivista]
R., Bucciardini; K., Pugliese; L., Weimer; M., Digregorio; V., Fragola; M., Mancini; Z., Maroccia; N., Ladisa; D., Francisci; R., Bellagamba; A., Degli Antoni; Guaraldi, Giovanni; O., Cirioni; F., Ortu; G., Parruti; M., Mannazzu; R., Libertone; S., Donnini; M., Floridia
abstract

BACKGROUND: Health-related quality of life (HRQoL) has been recognized as a central measure of the overall health status in HIV patients. With the availability of different highly effective drug combinations, maximizing quality-adjusted survival has become a major target of HIV treatment. Although the association of HIV RNA and CD4 cell count with clinical HIV progression has been well established, the relation between these markers and HRQoL measures is still unclear. METHOD: This cross-sectional study investigated the relationship linking HIV RNA and CD4 to HRQoL measures in 181 triple-class-experienced patients with advanced HIV disease. The instrument used was the ISSQoL, a self-administered and HIV-specific HRQoL questionnaire. RESULTS: Data showed no correlation between HRQoL measures and CD4 counts. Higher HIV RNA levels were, however, associated with poor HRQoL scores in 3 out of 9 scales of social functioning, depression and anxiety, and satisfaction with quality of life. In multivariable analyses, only the satisfaction with quality of life mean score remained significantly lower for the HIV RNA ≯100,000 copies/mL group compared to the HIV RNA 50 to 10,000 copies/mL group. CONCLUSIONS: Although other determinants of HRQoL in people with HIV should also be considered, this finding suggests a negative impact of high viral load on perceived HRQoL that adds to other described determinants of lower quality of life in people with HIV, such as lower social support and self-reported symptoms.

2014 - Relationship between testosterone and HIV-related comorbidities: secondary hypogonadism is associated with a poor health status in HIV-infected men [Abstract in Atti di Convegno]
Rochira, Vincenzo; Diazzi, Chiara; Brigante, Giulia; Santi, Daniele; Maria Chiara De, Caroli; Sara De, Vincentis; Simoni, Manuela; Carani, Cesare; Guaraldi, Giovanni
abstract

ABSTRACT INTRODUCTION: Testosterone (T) deficiency is very common in men with Human Immunodeficiency Virus (HIV), and it is more often associated with inappropriately low/normal luteinizing hormone (LH). However, the underlying causes remain poorly understood. Moreover, the role of HIV and/or HIV infection treatments, as well as the role of the general health status on the gonadal axis have been rarely investigated. AIM: The aim of this study is to evaluate the association between gonadal function and health status in men with HIV infection. METHODS: We performed a cross-sectional, observational study on 1359 consecutive HIV male outpatients. Morning serum Total T (TT), LH, estradiol, HIV parameters were measured. Frailty Index and number of comorbidities were extracted from the Clinical Database in which all patients data are recorded. TT<300 ng/dL was used as the threshold for biochemical T deficiency. RESULTS: T deficiency was found in 212 subjects (15.6%), and most of them (n=183; 13.4%) had secondary hypogonadism. TT resulted inversely related to Frailty Index in all patients (r=0.302, r2=0.091), this correlation being strengthened in HIV- infected men with secondary hypogonadism (r=0.403, r2=0.162). The percentage of HIVinfected men with TT <300 ng/dL increased progressively in accordance with the increase in the number of comorbidities (0.5%, 2.8%, 8.5%, 22.7%, 25.5%, 40% in men with 0, 1, 2, 3, 4, and >5 comorbidities, respectively). CONCLUSION: Poor health status in HIV-infected men might be involved in the pathogenesis of hypogonadism. This mechanism could reflect an adaptive response to illness in unhealthy patients similarly to what happens in other clinical conditions such as anorexia nervosa. Thus, low TT could be considered a biomarker of frailty and might confer an advantage for both the sick patients (in terms of sparing energy) and the species (preventing fatherhood). Furthermore, frailty related hypogonadism could be part of the process of premature aging already demonstrated in HIVinfected patients.

2014 - Simplification to atazanavir/ritonavir monotherapy for HIV-1 treated individuals on virological suppression: 48-week efficacy and safety results [Articolo su rivista]
Castagna, A.; Spagnuolo, V.; Galli, L.; Vinci, C.; Nozza, S.; Carini, E.; Monforte, A. D.; Montella, F.; Antinori, A.; Di Biagio, A.; Rusconi, S.; Lazzarin, A.; Viscoli, C.; Parisini, A.; Prinapori, R.; Mazzotta, F.; Lo Caputo, S.; Di Pietro, M.; D'Arminio-Monforte, A.; Tincati, C.; Bini, T.; Merlini, E.; Puoti, M.; Moioli, M.; Montella, M.; Di Sora, F.; Ammassari, A.; Ottou, S.; Cauda, R.; Di Giambenedetto, S.; Galli, M.; Franzetti, M.; Rizzardini, G.; Capetti, A.; Cossarini, F.; Gianotti, N.; Mussini, C.; Guaraldi, G.
abstract

Objectives: The objective of this study was to assess the 48-week virological efficacy of atazanavir/ritonavir (ATV/r) monotherapy vs. ATV/r along with two nucleoside reverse transcriptase (NRTIs) in HIV-1 treated individuals with HIV-RNA less than 50 copies/ml. Methods: A multicentre, randomized, open-label, noninferiority trial. HIV-1 treated individuals on ATV/r 300/100mg along with two NRTIs were randomized to receive ATV/r monotherapy or to maintain their antiretroviral regimen. The primary endpoint was the confirmed viral rebound (CVR: Two consecutive HIV-RNA &gt;50 copies/ml) or treatment discontinuation for any reason. Individuals who experienced CVR on ATV/r monotherapy reintroduced NRTIs and discontinued the study if HIV-RNA was more than 50 copies/ml after 12 weeks since reintensification. Results: One hundred and three patients enrolled. By week 48, 11 patients in ATV/r arm and two in ATV/r along with twoNRTIs experienced CVR; four (8%) patients in ATV/r and eight (15%) in ATV/r along with twoNRTIs discontinued. At the 48-week primary efficacy analysis (re-intensification=failure), treatment success was73%inATV/r armand85%in ATV/r along with two NRTIs [difference 12.1%, 95% confidence interval (95% CI)27.8 to 2.1]. According to the analysis considering re-intensification is equal to success, treatment success was 92%in ATV/r armand 85%in the ATV/r along with twoNRTIs arm (difference 7.5%, 95%CI4.7 to 19.8). At CVR, no mutation was observed in ATV/r arm and reintensification with NRTIs was effective in all individuals. Overall, Grade 3-4 (P=0.003) and grade 3-4 drug-related (P=0.027) adverse events were less frequent in ATV/r arm. A significant increase in total and low-density lipoprotein (LDL)-cholesterol was observed as well as a significant improvement in high-density lipoprotein (HDL)- cholesterol, fasting glucose, liver fibrosis and alkaline phosphatase was observed in ATV/r monotherapy in comparison with ATV/r along with two NRTIs. Conclusion: ATV/r monotherapy treatment simplification showed lower virological efficacy in comparison with maintaining triple therapy; NRTIs reintroduction was effective in all the individuals.

2014 - Surrogate markers of visceral adipose tissue in treated HIV-infected patients: accuracy of waist circumference determination [Articolo su rivista]
J., Falutz; L., Rosenthall; D., Kotler; Zona, Stefano; Guaraldi, Giovanni
abstract

Objectives: The accuracy of the use of anthropometrics to quantify visceral adipose tissue (VAT) in treated HIV-infected patients is unknown. We evaluated the predictive accuracy of waist circumference (WC) with and without dual-energy X-ray absorptiometry (DXA)-derived trunk:limb fat ratio [fat mass ratio (FMR)] as surrogates for VAT determined using computerized axial tomography (CT-determined VAT). Methods: We performed a retrospective cohort analysis of treated HIV-infected male patients followed at the Modena HIV Clinic. We developed prediction equations for VAT using linear regression analysis and Spearman correlations. Receiver operating characteristic (ROC) analysis evaluated the accuracy of WC alone or with FMR at discrete VAT thresholds. Results: The 1500 Caucasian male patients had a median age of 45 years, body mass index (BMI) of 24, WC of 87cm, VAT area of 127cm2 and body fat percentage of 14%. The correlation between WC-predicted VAT and CT-VAT was 0.613, and this increased significantly if FMR was added. The WC-associated R2 of 0.35 increased to 0.51 if the prediction equation included WC plus FMR. The area under the ROC curve (AUC) using WC was 0.795-0.820 at all VAT thresholds. The positive predictive value (PPV) and negative predictive value (NPV) changed reciprocally at CT-VAT thresholds from 75 to 200cm2 and ranged from 0.72 to 0.74, respectively, at a representative VAT of 125cm2. Adding the FMR to the predictive equations increased the AUC in the range of 0.854-0.889 with the PPV and NPV increasing minimally, ranging from 0.780 to 0.821. Limits of precision were wide, especially at the highest CT-VAT levels, and varied from 24 to 68cm2. Conclusions: WC is a limited surrogate for CT-VAT in this population and DXA-derived parameters do not improve performance indices to a clinically relevant level. These findings should inform the applicability of WC to predict VAT in treated HIV-infected male patients. © 2013 British HIV Association.

2014 - Switching to darunavir/ritonavir monotherapy vs. triple-therapy on body fat redistribution and bone mass in HIV-infected adults: Monarch randomized controlled trial [Articolo su rivista]
Guaraldi, Giovanni; Zona, Stefano; Cossarizza, Andrea; L., Vernacotola; Carli, Federica; A., Lattanzi; Nardini, Giulia; Orlando, Gabriella; E., Garlassi; R., Termini; M., Garau
abstract

BackgroundChanges in body fat distribution and bone mass in HIV-infected patients may be associated with long-term use of nucleoside analogues.MethodsThe Monarch trial recruited 30 patients receiving non-nucleoside reverse transcriptase inhibitor or protease inhibitor-based highly active antiretroviral therapy, with HIV RNA <40 copies/mL. Patients were randomized to either darunavir/ritonavir 800/100 mg once daily monotherapy or darunavir/ritonavir 800/100 mg once daily + 2NRTIs. Bone mass, peripheral lipoatrophy and central fat accumulation were assessed using dual-energy X-ray absorptiometry scanning, supplemented by computed tomography scans.ResultsMedian age was 43 years, 77% were males. Visceral adipose tissue remained stable from baseline to Week 48 in the whole group (p = 0.261) with no significant difference between arms (p = 0.56). There was a significant reduction in insulin resistance (HOMA-IR, p = 0.013) over 48 weeks in the whole group, but not of body mass index (p = 0.24). In the darunavir/ritonavir monotherapy arm, there was a small but significant increase in both lumbar and femur bone mineral density at 48 weeks and was observed after correction for baseline values. The absolute change in lumbar bone mineral density at 48 weeks was more pronounced in the darunavir/ritonavir arm compared with the darunavir/ritonavir + 2NRTIs arm.ConclusionsIn this study, discontinuing nucleoside analogues and switching to darunavir/ritonavir monotherapy was associated with a small but statistically significant increase in bone mineral density, but stable levels of limb fat and visceral adipose tissue.

2014 - The Burden of Image Based Emphysema and Bronchiolitis in HIV-Infected Individuals on Antiretroviral Therapy [Articolo su rivista]
Guaraldi, Giovanni; Besutti, Giulia; Scaglioni, Riccardo; Santoro, Antonella; Zona, Stefano; Ligabue, Guido; Marchioni, Alessandro; Orlando, Gabriella; Carli, Federica; Beghe', Bianca; Fabbri, Leonardo; J., Leipsic; D., Don Sin; S. F. P., Man
abstract

Abstract Background: With the widespread use of anti-retroviral therapy (ART), individuals infected with human immune deficiency virus (HIV) are increasingly experiencing morbidity and mortality from respiratory disorders. However, the prevalence or the risk factors associated with emphysema and bronchiolitis are largely unknown. Methods: Thoracic computed tomography (CT) scans were performed in 1,446 patients infected with HIV who were on ART and who attended a tertiary care metabolic clinic (average age 48 years and 29% females). Detailed history and physical examination including anthropometric measurements were performed. Complete pulmonary function tests were performed in a subset of these patients (n = 364). No subjects were acutely ill with a respiratory condition at the time of CT scanning. Findings: Nearly 50% of the subjects had CT evidence for emphysema, bronchiolitis or both with 13% (n = 195) showing bronchiolitis, 19% (n = 274) showing emphysema and 16% (n = 238) revealing both. These phenotypes were synergistically associated with reduced regular physical activity (p for interaction ,.0001). The most significant risk factors for both phenotypes were cigarette smoking, intravenous drug use and peripheral leucocytosis. Together, the area-under-the curve statistics was 0.713 (p = 0.0037) for discriminating those with and without these phenotypes. There were no significant changes in lung volumes or flow rates related to these phenotypes, though the carbon monoxide diffusion capacity was reduced for the emphysema phenotype. Interpretation: Emphysema and bronchiolitis are extremely common in HIV-infected patients who are treated with ART and can be identified by use of thoracic CT scanning.

2014 - The natural history of HIV-associated lipodystrophy in the changing scenario of HIV infection [Articolo su rivista]
Guaraldi, Giovanni; Stentarelli, Chiara; Zona, Stefano; A., Santoro; Beghetto, Barbara; Carli, Federica; Orlando, Gabriella; Franceschetto, Antonella; A., Casolo; Mussini, Cristina
abstract

Objectives: In long-term HIV-infected patients, peripheral lipoatrophy (LA) and central lipohypertrophy (LH) appear to be related to the same insults (virus and antiretroviral drugs), but are likely to be associated with different fat depot physiologies. The objective of this study was to describe the natural history of lipodystrophy assessed using dual energy X-ray absorptiometry (DEXA) and computed tomography (CT) in a large HIV out-patients metabolic clinic. Methods: An observational retrospective study was carried out including HIV-infected patients recruited at the Metabolic Clinic of Modena, Modena, Italy, who were assessed for lipodystrophy and had at least two anthropometric evaluations using DEXA for leg fat per cent mass and abdominal CT for visceral adipose tissue (VAT). Factors associated with leg fat per cent and VAT changes were analysed using multivariable generalized estimating equation (GEE) regression models. Results: A total of 6789 DEXAs and 7566 CT scans were evaluated in the observation period. A total of 1840 patients were included; the mean age was 45.2±7.2 (standard deviation) years, 621 (34%) were women, and the median HIV infection duration was 176 (interquartile range 121-232) years. According to the GEE multivariable regression analysis, leg fat per cent evaluated with DEXA appeared to increase over calendar years (ß=0.92; P<0.001); moreover, a progressive increase in VAT was observed in the cohort (ß=5.69; P<0.001). No association with antiretroviral drugs was found. Conclusions: In our study, neither LA nor LH appeared to be associated with antiretroviral drug exposure. We observed a progressive increase in LH in HIV-infected patients over calendar years. This anthropometric change, together with loss of appendicular lean mass, could describe a physiological aging process in HIV-infected patients.

2014 - Urolithiasis associated with atazanavir may mask a metabolic 'channelling' bias. [Articolo su rivista]
Guaraldi, Giovanni; Dolci, G; Bellasi, A.
abstract

n/a

2013 - Associatioin of epicardial adipose tissue with incident coronary heart disease and death in HIV infected patients. [Abstract in Rivista]
Guaraldi, Giovanni; Scaglioni, Riccardo; Zona, Stefano; Orlando, Gabriella; Carli, Federica; Ligabue, Guido; Besutti, Giulia; Menozzi, Marianna; Santoro, Antonella; Beghetto, Barbara; Mussini, Cristina; P., Raggi
abstract

Epicardial adipose tissue has been reported to be highly inflamed and to be associated with incident coronary artery disease and all cause mortality in the general population. Its association with adverse events in HIV is unknown.

2013 - Birth defects in a national cohort of pregnant women with HIV infection in Italy, 2001-2011 [Articolo su rivista]
Floridia, M.; Mastroiacovo, P.; Tamburrini, E.; Tibaldi, C.; Todros, T.; Crepaldi, A.; Sansone, M.; Fiscon, M.; Liuzzi, G.; Guerra, B.; Vimercati, A.; Vichi, F.; Vicini, I.; Pinnetti, C.; Marconi, A. M.; Ravizza, M.; Mori, F.; Ortolani, P.; dalle Nogare, E. R.; Di Lorenzo, F.; Sterrantino, G.; Meli, M.; Polemi, S.; Nocentini, J.; Baldini, M.; Montorzi, G.; Mazzetti, M.; Rogasi, P.; Borchi, B.; Pinter, E.; Anzalone, E.; Marocco, R.; Mastroianni, C.; Mercurio, V. S.; Carocci, A.; Grilli, E.; Maccabruni, A.; Zaramella, M.; Mariani, B.; Natalini Raponi, G.; Guaraldi, G.; Luzi, K.; Nardini, G.; Stentarelli, C.; Degli Antoni, A. M.; Molinari, A.; Crisalli, M. P.; Donisi, A.; Piepoli, M.; Cerri, V.; Zuccotti, G.; Giacomet, V.; Fabiano, V.; Coletto, S.; Placido, G.; Vivarelli, A.; Castelli, P.; Savalli, F.; Portelli, V.; Sabbatini, F.; Francisci, D.; Bernini, L.; Alberico, S.; Maso, G.; Tropea, M.; Meloni, A.; Dedoni, M.; Cuboni, C.; Ortu, F.; Piano, P.; Citernesi, A.; Spinillo, A.; Roccio, M.; Miccolis, A.; Bassi, E.; Cervi, F.; Puccetti, C.; Murano, P.; Contoli, M.; Capretti, M. G.; Marsico, C.; Faldella, G.; Martinelli, P.; Agangi, A.; Trentini, L.; Masuelli, G.; Garetto, S.; Cetin, I.; Brambilla, T.; Savasi, V.; Giaquinto, C.; Rinaldi, R.; Rubino, E.; Bucceri, A.; Matrone, R.; Scaravelli, G.; Fundaro, C.; Genovese, O.; Cafforio, C.; Tozzi, V.; Massetti, P.; Anceschi, M.; Casadei, A. M.; Cavaliere, A. F.; Finelli, V.; Cellini, M.; Castelli Gattinara, G.; Dalzero, S.; Sacchi, V.; De Pirro, A.; Polizzi, C.; Mattei, A.; Pirillo, M. F.; Amici, R.; Galluzzo, C. M.; Donnini, S.; Baroncelli, S.; Regazzi, M.; Villani, P.; Cusato, M.; Cerioli, A.; De Martino, M.; Moroni, M.; Parazzini, F.; Vella, S.
abstract

Objective: We used data from a national study of pregnant women with HIV to evaluate the prevalence of congenital abnormalities in newborns from women with HIV infection. Design: Observational study. Setting: University and hospital clinics. Population: Pregnant women with HIV exposed to antiretroviral treatment at any time during pregnancy. Methods: The total prevalence of birth defects was assessed on live births, stillbirths, and elective terminations for fetal anomaly. The associations between potentially predictive variables and the occurrence of birth defects were expressed as odds ratios (ORs) with 95% confidence intervals (95% CIs) for exposed versus unexposed cases, calculated in univariate and multivariate logistic regression analyses. Main outcome measures: Birth defects, defined according to the Antiretroviral Pregnancy Registry criteria. Results: A total of 1257 pregnancies with exposure at any time to antiretroviral therapy were evaluated. Forty-two cases with major defects were observed. The total prevalence was 3.2% (95% CI 1.9-4.5) for exposure to any antiretroviral drug during the first trimester (23 cases with defects) and 3.4% (95% CI 1.9-4.9) for no antiretroviral exposure during the first trimester (19 cases). No associations were found between major birth defects and first-trimester exposure to any antiretroviral treatment (OR 0.94, 95% CI 0.51-1.75), main drug classes (nucleoside reverse transcriptase inhibitors, OR 0.95, 95% CI 0.51-1.76; non-nucleoside reverse transcriptase inhibitors, OR 1.20, 95% CI 0.56-2.55; protease inhibitors, OR 0.92, 95% CI 0.43-1.95), and individual drugs, including efavirenz (prevalence for efavirenz, 2.5%). Conclusions: This study adds further support to the assumption that first-trimester exposure to antiretroviral treatment does not increase the risk of congenital abnormalities. © 2013 RCOG.

2013 - Body Mass Index and Weight Gain in Pregnant Women With HIV: A National Study in Italy [Articolo su rivista]
M., Floridia; M., Ravizza; G., Masuelli; S., Dalzero; C., Pinnetti; I., Cetin; A., Meloni; A., Spinillo; E., Rubino; D., Francisci; E., Tamburrini; M., Floridia; M., Ravizza; E., Tamburrini; F., Mori; P., Ortolani; E. R., dalle Nogare; F., Di Lorenzo; G., Sterrantino; M., Meli; S., Polemi; J., Nocentini; M., Baldini; G., Montorzi; M., Mazzetti; P., Rogasi; B., Borchi; F., Vichi; E., Pinter; E., Anzalone; R., Marocco; C., Mastroianni; V. S., Mercurio; A., Carocci; E., Grilli; A., Maccabruni; M., Zaramella; B., Mariani; G., Natalini Raponi; Guaraldi, Giovanni; K., Luzi; Nardini, Giulia; Stentarelli, Chiara; A. M., Degli Antoni; A., Molinari; M. P., Crisalli; A., Donisi; M., Piepoli; V., Cerri; G., Zuccotti; V., Giacomet; V., Fabiano; G., Placido; A., Vivarelli; P., Castelli; F., Savalli; V., Portelli; F., Sabbatini; D., Francisci; L., Bernini; S., Alberico; G., Maso; M., Tropea; A., Meloni; M., Dedoni; C., Cuboni; F., Ortu; P., Piano; A., Citernesi; I., Vicini; A., Spinillo; M., Roccio; A., Vimercati; A., Miccolis; E., Bassi; B., Guerra; F., Cervi; C., Puccetti; P., Murano; M., Contoli; M. G., Capretti; C., Marsico; G., Faldella; M., Sansone; P., Martinelli; A., Agangi; C., Tibaldi; L., Trentini; T., Todros; G., Masuelli; S., Garetto; I., Cetin; T., Brambilla; V., Savasi; A., Crepaldi; C., Giaquinto; M., Fiscon; R., Rinaldi; E., Rubino; A., Bucceri; R., Matrone; G., Scaravelli; C., Fundaro; O., Genovese; C., Cafforio; C., Pinnetti; G., Liuzzi; V., Tozzi; P., Massetti; M., Anceschi; A. M., Casadei; A. F., Cavaliere; V., Finelli; M., Cellini; G., Castelli Gattinara; A. M., Marconi; S., Dalzero; V., Sacchi; A., De Pirro; C., Polizzi; A., Mattei; M. F., Pirillo; R., Amici; C. M., Galluzzo; S., Donnini; S., Baroncelli; M., Floridia; P., Villani; M., Cusato; A., Cerioli; M., De Martino; P., Mastroiacovo; M., Moroni; F., Parazzini; E., Tamburrini; S., Vella; P., Martinelli
abstract

not available

2013 - CD8 T-Cell Activation Is Associated With Lipodystrophy and Visceral Fat Accumulation in Antiretroviral Therapy–Treated Virologically Suppressed HIV-Infected Patients [Articolo su rivista]
Guaraldi, Giovanni; Kety, Luzi; Giusi Maria, Bellistrì; Zona, Stefano; Ana Rita Domingues da, Silva; Francesca, Bai; Elisa, Garlassi; Giulia, Marchetti; Jacqueline, Capeau; Antonella d’Arminio, Monforte
abstract

OBJECTIVE.: HIV-infected patients receiving antiretroviral treatment frequently accumulate fat at the abdominal level. It is unknown whether T-cell activation and immune phenotypes are associated with fat accumulation. Thus, the aim of the study was to search for an association between the presence of clinical lipodystrophy (LD), visceral and subcutaneous abdominal adipose tissue amount (VAT and SAT) and peripheral T-cell immune phenotypes. DESIGN.: Cross-sectional study including 87 HIV-infected ART-treated, virologically-suppressed and immune-reconstituted patients. METHODS.: The patients were evaluated for clinical LD, VAT, SAT, insulin resistance (HOMA-IR) and coronary calcium score (CAC>10). T-cell activation (CD8/CD38), differentiation (CD4/CD8/CCR7/CD45RA) and expression/activation of the IL7/IL-7R system (CD4/CD8/CD127; IL-7; CD4/CD8/pStat-5) were assessed by cytometry. RESULTS.: In multivariable analyses CD8+T-cell activation (CD38+) was associated with lipoatrophy and central fat accumulation (respectively: ß=5.63; p=0.005; and: ß=4.19; p=0.020). This was also the case for IL-7R expressing CD8+T-cells (CD127+): respectively for lipoatrophy ß=12.8; p=0.003 and central fat accumulation ß=9.45; p=0.016. CD8+T-cell activation was also associated with VAT/TAT (ß= 0.01; p=0.002) and SAT/VAT ratios (ß= -0.014; p=0.015).As expected, VAT/TAT was an independent risk factor for insulin resistance (HOMA-IR, r=0.364, p=0.028) and cardiovascular risk (CAC, r=0.406, p=0.002). CONCLUSIONS.: CD8+T-cell activation was associated with lipodystrophy and the relative amount of VAT in ART-controlled, virologically-suppressed, HIV-infected patients. We propose that CD8 activation may be involved in the accumulation of central fat frequently observed in these patients, with resulting increased cardio-metabolic risk.

2013 - Changing scenarios of HIV treatment in Southern Africa [Capitolo/Saggio]
Guaraldi, Giovanni; Puzzolante, Cinzia; C., Lazzaretti; A., Santoro; Guaraldi, Francesco
abstract

In this paper we will analyse the assesment criteria for road map to control the HIV pandemic in SSA within the context of the changing scenarios of HIV disease in the third millennium. They include: effective medical interventions; political will; community participation

2013 - Characteristics of HIV-infected patients not retained in care of two cohorts of northern Italy. [Abstract in Rivista]
Franceschini, Erica; Zona, Stefano; V., Borghi; T., Bini; P., Cicconi; Guaraldi, Giovanni; A., D’Arminio Monforte; Mussini, Cristina
abstract

The aim of the study was to assess the proportion of patients not-retained in care after HIV diagnosis in two cohorts of Northern Italy.

2013 - Characterization of Specific Immune Responses to Different Aspergillus Antigens during the Course of Invasive Aspergillosis in Hematologic Patients [Articolo su rivista]
Potenza, Leonardo; Vallerini, Daniela; Barozzi, Patrizia; Riva, Giovanni; Forghieri, Fabio; Beauvais, Anne; Beau, Remi; Candoni, Anna; Maertens, Johan; Rossi, Giulio; Morselli, Monica; Zanetti, Eleonora; Quadrelli, Chiara; Codeluppi, Mauro; Guaraldi, Giovanni; Pagano, Livio; Caira, Morena; DEL GIOVANE, Cinzia; Maccaferri, Monica; Stefani, Alessandro; Morandi, Uliano; Tazzioli, Giovanni; Girardis, Massimo; Delia, Mario; Specchia, Giorgina; Longo, Giuseppe; Marasca, Roberto; Narni, Franco; Merli, Francesco; Imovilli, Annalisa; Apolone, Giovanni; Carvalho, Agostinho; Comoli, Patrizia; Romani, Luigina; Latgè, Jean Paul; Luppi, Mario
abstract

Several studies in mouse model of invasive aspergillosis (IA) and in healthy donors have shown that different Aspergillus antigens may stimulate different adaptive immune responses. However, the occurrence of Aspergillus-specific T cells have not yet been reported in patients with the disease. In patients with IA, we have investigated during the infection: a) whether and how specific T-cell responses to different Aspergillus antigens occur and develop; b) which antigens elicit the highest frequencies of protective immune responses and, c) whether such protective T cells could be expanded ex-vivo. Forty hematologic patients have been studied, including 22 patients with IA and 18 controls. Specific T cells producing IL-10, IFN-γ, IL-4 and IL-17A have been characterized through enzyme linked immunospot and cytokine secretion assays on 88 peripheral blood (PB) samples, by using the following recombinant antigens: GEL1p, CRF1p, PEP1p, SOD1p, α1-3glucan, β1-3glucan, galactomannan. Specific T cells were expanded through short term culture. Aspergillus-specific T cells producing non-protective interleukin-10 (IL-10) and protective interferon-gamma (IFN-γ) have been detected to all the antigens only in IA patients. Lower numbers of specific T cells producing IL-4 and IL-17A have also been shown. Protective T cells targeted predominantly Aspergillus cell wall antigens, tended to increase during the IA course and to be associated with a better clinical outcome. Aspergillus-specific T cells could be successfully generated from the PB of 8 out of 8 patients with IA and included cytotoxic subsets able to lyse Aspergillus hyphae. Aspergillus specific T-cell responses contribute to the clearance of the pathogen in immunosuppressed patients with IA and Aspergillus cell wall antigens are those mainly targeted by protective immune responses. Cytotoxic specific T cells can be expanded from immunosuppressed patients even during the infection by using the above mentioned antigens. These findings may be exploited for immunotherapeutic purposes in patients with IA. © 2013 Potenza et al.

2013 - Combined Use of Waist and Hip Circumference to Identify Abdominally Obese HIV-Infected Patients at Increased Health Risk [Articolo su rivista]
Trevor, O’Neill; Guaraldi, Giovanni; Orlando, Gabriella; Carli, Federica; Garlassi, Elisa; Zona, Stefano; Jean Pierre, Després; Robert, Ross
abstract

OBJECTIVES: To determine whether for a given waist circumference (WC), a larger hip circumference (HC) was associated with a reduced risk of insulin resistance, type 2 diabetes (T2D), hypertension and cardiovascular disease (CVD) in HIV-infected patients. A second objective was to determine whether, for a given WC, the addition of HC improved upon estimates of abdominal adiposity, in particular visceral adipose tissue (VAT), compared to those obtained by WC alone. METHODS: HIV-infected men (N = 1481) and women (N = 841) were recruited between 2005 and 2009. WC and HC were obtained using standard techniques and abdominal adiposity was measured using computed tomography. RESULTS: After control for WC and covariates, HC was negatively associated with risk of insulin resistance (p<0.05) and T2D [Men: OR = 0.91 (95% CI: 0.86-0.96); Women: OR = 0.91 (95% CI: 0.84-0.98)]. For a given WC, HC was also negatively associated with a lower risk of hypertension (p<0.05) and CVD [OR = 0.94 (95% CI: 0.88-0.99)] in men, but not women. Although HC was negatively associated with VAT in men and women after control for WC (p<0.05), the addition of HC did not substantially improve upon the prediction of VAT compared to WC alone. CONCLUSIONS: The identification of HIV-infected individuals at increased health risk by WC alone is substantially improved by the addition of HC. Estimates of visceral adipose tissue by WC are not substantially improved by the addition of HC and thus variation in visceral adiposity may not be the conduit by which HC identifies increased health risk.

2013 - Contribution of Genetic Background, Traditional Risk Factors, and HIV-Related Factors to Coronary Artery Disease Events in HIV-Positive Persons [Articolo su rivista]
M., Rotger; T. R., Glass; T., Junier; J., Lundgren; J. D., Neaton; E. S., Poloni; A. B., van 't Wout; R., Lubomirov; S., Colombo; R., Martinez; A., Rauch; H. F., Gunthard; J., Neuhaus; D., Wentworth; D., van Manen; L. A., Gras; H., Schuitemaker; L., Albini; C., Torti; L. P., Jacobson; X., Li; L. A., Kingsley; Carli, Federica; Guaraldi, Giovanni; E. S., Ford; I., Sereti; C., Hadigan; E., Martinez; M., Arnedo; L., Egana Gorrono; J. M., Gatell; M., Law; C., Bendall; K., Petoumenos; J., Rockstroh; J. C., Wasmuth; K., Kabamba; M., Delforge; S., De Wit; F., Berger; S., Mauss; M., de Paz Sierra; M., Losso; W. H., Belloso; M., Leyes; A., Campins; A., Mondi; A., De Luca; I., Bernardino; M., Barriuso Iglesias; A., Torrecilla Rodriguez; J., Gonzalez Garcia; J. R., Arribas; I., Fanti; S., Gel; J., Puig; E., Negredo; M., Gutierrez; P., Domingo; J., Fischer; G., Fatkenheuer; C., Alonso Villaverde; A., Macken; J., Woo; T., Mcginty; P., Mallon; A., Mangili; S., Skinner; C. A., Wanke; P., Reiss; R., Weber; H. C., Bucher; J., Fellay; A., Telenti; P. E., Tarr
abstract

BACKGROUND: Persons infected with human immunodeficiency virus (HIV) have increased rates of coronary artery disease (CAD). The relative contribution of genetic background, HIV-related factors, antiretroviral medications, and traditional risk factors to CAD has not been fully evaluated in the setting of HIV infection. METHODS: In the general population, 23 common single-nucleotide polymorphisms (SNPs) were shown to be associated with CAD through genome-wide association analysis. Using the Metabochip, we genotyped 1875 HIV-positive, white individuals enrolled in 24 HIV observational studies, including 571 participants with a first CAD event during the 9-year study period and 1304 controls matched on sex and cohort. RESULTS: A genetic risk score built from 23 CAD-associated SNPs contributed significantly to CAD (P = 2.9 × 10(-4)). In the final multivariable model, participants with an unfavorable genetic background (top genetic score quartile) had a CAD odds ratio (OR) of 1.47 (95% confidence interval [CI], 1.05-2.04). This effect was similar to hypertension (OR = 1.36; 95% CI, 1.06-1.73), hypercholesterolemia (OR = 1.51; 95% CI, 1.16-1.96), diabetes (OR = 1.66; 95% CI, 1.10-2.49), ≥ 1 year lopinavir exposure (OR = 1.36; 95% CI, 1.06-1.73), and current abacavir treatment (OR = 1.56; 95% CI, 1.17-2.07). The effect of the genetic risk score was additive to the effect of nongenetic CAD risk factors, and did not change after adjustment for family history of CAD. CONCLUSIONS: In the setting of HIV infection, the effect of an unfavorable genetic background was similar to traditional CAD risk factors and certain adverse antiretroviral exposures. Genetic testing may provide prognostic information complementary to family history of CAD.

2013 - Cost of noninfectious comorbidities in patients with HIV [Articolo su rivista]
Guaraldi, Giovanni; Zona, Stefano; Menozzi, Marianna; Carli, Federica; Bagni, Pietro; Berti, A; Rossi, E; Orlando, Gabriella; Zoboli, G; Palella, F.
abstract

OBJECTIVES: We hypothesized that the increased prevalence of noninfectious comorbidities (NICMs) observed among HIV-infected patients may result in increased direct costs of medical care compared to the general population. Our objective was to provide estimates of and describe factors contributing to direct costs for medical care among HIV-infected patients, focusing on NICM care expenditure. METHODS: A case-control study analyzing direct medical care costs in 2009. Antiretroviral therapy (ART)-experienced HIV-infected patients (cases) were compared to age, sex, and race-matched adults from the general population, included in the CINECA ARNO database (controls). NICMs evaluated included cardiovascular disease, hypertension, diabetes mellitus, bone fractures, and renal failure. Medical care cost information evaluated included pharmacy, outpatient, and inpatient hospital expenditures. Linear regression models were constructed to evaluate predictors of total care cost for the controls and cases. RESULTS: There were 2854 cases and 8562 controls. Mean age was 46 years and 37% were women. We analyzed data from 29,275 drug prescription records. Positive predictors of health care cost in the overall population: HIV infection (β = 2878; confidence interval (CI) = 2001-3755); polypathology (β = 8911; CI = 8356-9466); age (β = 62; CI = 45-79); and ART exposure (β = 18,773; CI = 17,873-19,672). Predictors of health care cost among cases: Center for Disease Control group C (β = 1548; CI = 330-2766); polypathology (β = 11,081; CI = 9447-12,716); age < 50 years (β = 1903; CI = 542-3264); protease inhibitor exposure (per month of use; β = 69; CI = 53-85); CD4 count < 200 cells/mm3 (β = 5438; CI = 3082-7795); and ART drug change (per change; β = 911; CI = 716-1106). CONCLUSION: Total cost of medical care is higher in cases than controls. Lower medical costs associated with higher CD4 strata are offset by increases in the care costs needed for advancing age, particularly for NICMs.

2013 - Does lipohypertrophy increase cardiovascular risk? Assessing patients for metabolic disordes [Capitolo/Saggio]
Guaraldi, Giovanni
abstract

not available

2013 - Effects of gender and body composition on GH response to GHRH plus Arginine (GHRH+ARG) in HIV-lipodystrophic patients [Abstract in Rivista]
Brigante, Giulia; Diazzi, Chiara; G., Ferrannini; Ansaloni, Anna; Zirilli, Lucia; Guaraldi, Giovanni; Rochira, Vincenzo
abstract

GH-deficiency is more frequent in men with HIV than in HIV-infected women.

2013 - Effects of gender and body composition on GH response to GHRH plus Arginine (GHRH+Arg) in HIV-lipodystrophic patients: higher rate of GH deficiency in men. [Abstract in Rivista]
Brigante, Giulia; Diazzi, Chiara; G., Ferrannini; Ansaloni, Anna; Zirilli, Lucia; Carani, Cesare; Guaraldi, Giovanni; Rochira, Vincenzo
abstract

The study investigates gender differences in the rate of GH-deficiency among hIV-infected men.

2013 - Effects of gender and body composition on GH response to GHRH+Arg in HIV-lipodystrophic patients: higher rate of GH deficiency in men [Abstract in Rivista]
Brigante, Giulia; Diazzi, Chiara; Giulia, Ferrannini; Ansaloni, Anna; Zirilli, Lucia; Guaraldi, Giovanni; Rochira, Vincenzo
abstract

The study investigated the gender difference in GH secretion after GHRH+Arg in patients with HIV-related lipodystrophy showing hoe men are at higher risk to fail to respond copmared to females. In this group of patients with HIV that are at higher risk of GH deficiency, men have higher risk of GH deficiency than women.

2013 - Effects of pregnancy on endothelial function and cardiovascular disease risk in HIV-infected women [Articolo su rivista]
K., Luzi; A. R., Eckard; A., Lattanzi; ZONA, Stefano; MODENA, Maria Grazia; FACCHINETTI, Fabio; GUARALDI, Giovanni
abstract

– This study assessed flow–mediated vasodilation (FMD) and brachial artery diameter (BAD) in HIV–infected pregnant women compared to healthy pregnant controls, and determined their relationships to variables of interest, including the HIV status. No differences were observed in FMD or BAD between HIV–infected and healthy pregnant women, and neither measure changed significantly during pregnancy. HIV status did not affect endothelial function or brachial artery diameter. Pregnancy does not appear to further increase the CVD risk associated with HIV infection.

2013 - Efficacy and safety of Nevirapine plus raltegravir as dual regimen in the clinical setting [Abstract in Rivista]
C., Montrucchio; A., Calcagno; A., Capetti; Guaraldi, Giovanni; G., Cenderello; L., Calza; M., Lanzafame; L., Marinaro; M. C., Tettoni; L., Trentini; G., Di Perri; S., Bonora
abstract

Dual therapy based on raltegravir and nevirapine has been recently proposed as a possible switching strategy in selected patients, due to attractive tolerability and safety profile. We recently reported the pharmacokinetic compatibility of these drugs when administered twice-daily, but data on efficacy and safety of this combination in the clinical setting are scarce.

2013 - Emphysema is an independent predictor of coronary artery calcium score in a large cohort of HIV infected patients [Abstract in Atti di Convegno]
Guaraldi, Giovanni; Besutti, Giulia; Scaglioni, Riccardo; Santoro, Antonella; Zona, Stefano; Ligabue, Guido; Orlando, Gabriella; Carli, Federica; Mussini, Cristina; J. Leipsic D. D., Sin; S. F. P., Man
abstract

The objective of this study was to evaluate the association between emphysema and CAC in a large cohort of HIV infected patients undergoing ART

2013 - Emphysema is an independent predictor of coronary artery calcium score in a large cohort of HIV-infected patients. [Abstract in Rivista]
Guaraldi, Giovanni; Besutti, Giulia; Scaglioni, Riccardo; Santoro, Antonella; Zona, Stefano; Ligabue, Guido; Mussini, Cristina; Orlando, Gabriella; Carli, Federica; J., Lipsic; D. D., Sin; S. F. P., Man
abstract

The complex relationship between chronic obstructive pulmonary disease and cardiovascular disease has not been investigated in patients chronically infected with HIV. The objective of this study was to evaluate the association between emphysema and coronary artery calcium score as surrogate for coronary artery diasease in a large cohort of HIV-infected patients on antiretroviral treatment.

2013 - HIGH PREVALENCE OF VITAMIN D DEFICIENCY IN A COHORT OF HIV INFECTED PREGNANT AND NON-PREGNANT WOMEN OF CHILDBEARING AGE [Poster]
Stentarelli, Chiara; Zona, Stefano; E., Garlassi; Menozzi, Marianna; T., Trenti; S., Baroncelli; C., Pinnetti; A., Degli Antoni; M., Floridia; Guaraldi, Giovanni
abstract

Aims: To analyze prevalence and risk factors for 25(OH) VitaminD [25(OH)D] plasma levels < 20ng/mL among HIV-infected pregnant and non-pregnant women. Methods: Cross-sectional, case-control study comparing HIV-infected pregnant women at third trimester enrolled between 2003 and 2010 in the Italian National Program on Surveillance on Antiretroviral Treatment in Pregnancy and HIV-infected non-pregnant women followed within the Modena Metabolic Clinic. The two groups were matched for age, seasonality of 25(OH)D measurement and body mass index. Quantitative determinations of 25(OH)D were measured using chemiluminescent immunoassay (CLIA) technology. Results: Two hundred twelve HIV-infected women were studied. African ethnicity was more common in the group of pregnant women (37.6% vs.10.5%). Two groups had similar prevalence of 25(OH)D levels < 20ng/mL (64.1% vs. 54.7%, respectively; p=0.166). At univariate logistic regression analysis, only black ethnicity was found to be different in two study groups (0.015). Multivariate analysis is shown in table1. Conclusion: This study shows a high prevalence of vitaminD deficiency in both groups. Pregnancy per se didn't result an independent risk factor for vitamin D deficiency. Both groups recognized traditional risk factors for vitaminD deficiency

2013 - HIGH PREVALENCE OF VITAMIN D DEFICIENCY IN A COHORT OF HIV INFECTED PREGNANT WOMEN AND ITS IMPACT ON PREGNANCY OUTCOME [Poster]
Stentarelli, Chiara; Zona, Stefano; E., Garlassi; Menozzi, Marianna; T., Trenti; S., Baroncelli; C., Pinnetti; A., Degli Antoni; M., Floridia; Guaraldi, Giovanni
abstract

Background and aims: To assess out the clinical impact of 25(OH)D plasma levels < 20ng/mL in HIV-infected pregnant women and their newborns. Methods: Cross-sectional study. Quantitative determinations of 25(OH)D were measured using chemiluminescent immunoassay technology in HIV-infected pregnant women at third trimester, participating between 2003 and 2010 to the Italian National Program on Surveillance on Antiretroviral Treatment in Pregnancy. Results: One hundred seventeen HIV-infected pregnant women were studied. 25(OH)D mean value(±SD) was 19.89(±11.36)ng/mL. Prevalence of 25(OH)D levels < 20ng/mL was 64.1%. Preterm delivery (< 37weeks) occurred in 15.38% of the women. There was no statistically significant association between low 25(OH)D and pregnancy outcomes at multivariate analysis (Table1). Conclusion: This study shows a high prevalence of 25(OH)D deficiency. Future studies are needed to verify potential role of low 25(OH)D in determining birth weight in HIV-infected pregnant women.

2013 - HIV-Associated Lipodystrophy: Impact of Antiretroviral Therapy [Articolo su rivista]
Guaraldi, Giovanni; Stentarelli, Chiara; Zona, Stefano; Antonella, Santoro
abstract

In the late 1990s, reports of unusual changes in body fat distribution named ‘lipodystrophy’ (LD) began to appear in HIV patients mitigating the enormous enthusiasm about improvement of survival and quality of life provided by the combinations of antiretroviral (ARV) drug classes, the so-called highly active antiretroviral therapy (HAART), which had just become available at that time. The objective of this paper is to critically review the literature on LD and to discuss the impact of newer ARV agents, namely atazanavir, darunavir and raltegravir, as well as strategies of the late HAART era, including single-tablet regimens and nucleoside-sparing regimens. Studies in which LD was measured by dual-energy x-ray absorptiometry or by abdominal computed tomography or magnetic resonance imaging scan only, were included. We were unable to identify studies depicting a negative impact of drugs or ARV regimens on limb fat loss. On the contrary, a few studies identified a negative impact of atazanavir/ritonavir or darunavir/ritonavir on trunk fat increase. It should be noted that this anthropometric measure is a poor instrument since it cannot distinguish between subcutaneous and visceral fat. We conclude that presumably the body fat changes currently observed in HIV-infected patients is the net result of competing phenomena: on one side the natural history of lipohypertrophy as a result of HIV and HAART impact, and on the other side the physiological body fat changes observed in the aging population.

2013 - Il ruolo dell’ageing, delle interazioni farmacologiche e comorbidità nella gestione a lungo termine del paziente HIV positivo. L’invecchiamento come variabile sempre più frequente nella gestione del paziente HIV positivo [Articolo su rivista]
Guaraldi, Giovanni
abstract

na

2013 - Inverse correlation between vascular calcification and bone mineral density in human immunodeficiency virus-infected patients [Articolo su rivista]
Antonio, Bellasi; Zona, Stefano; Orlando, Gabriella; Carli, Federica; Ligabue, Guido; Rochira, Vincenzo; Antonello, Santoro; Mussini, Cristina; Guaraldi, Giovanni; Paolo, Raggi
abstract

HIV-infected individuals suffer from acceler- ated aging, which manifests as premature cardiovascular and bone disease. However, little is known of the association of these two disorders in the HIV population. Our objective was to investigate the association between a marker of ath- erosclerosis (coronary artery calcium [CAC]) and low bone mineral density (BMD) in a cross-sectional cohort of HIV- infected patients. The study was conducted at the University of Modena and Reggio Emilia, Italy. A total of 636 con- secutive middle-aged, HIV-infected subjects were recruited between January 2006 and December 2010. All patients underwent CAC and BMD assessment. Patients were cate- gorized according to a CAC score\100 or[100 units based on previous literature that identified this cut-point as a marker of increased risk. Low femoral and lumbar spine BMD was defined as \25th percentile value for the study cohort. Logistic regression and bootstrap analysis were used to assess the independent association between CAC and BMD. The main outcome measure was a CAC score[100. Patients with CAC [ 100 were older and more likely to be men, diabetic, and overweight. Patients with CAC \ 100 had better renal function and a lower cardiovascular risk profile. After adjusting for age, sex, traditional and HIV- specific risk factors, vitamin D level, and PTH level, there was a significant association between CAC [ 100 and low BMD for the femur (OR = 2.33, 95 % CI 1.09–4.99; p = 0.02) but not for the spine. Bootstrap analyses con- firmed these findings. In summary, CAC was independently associated with low femoral BMD in HIV-infected patients. Future studies should test whether therapies that attenuate cardiovascular risk in HIV favorably impact bone health.

2013 - La malattia cardiovascolare in HIV:l'attenzione al paziente [Articolo su rivista]
Guaraldi, Giovanni
abstract

not available

2013 - La sindrome Lipodistrofica [Capitolo/Saggio]
Guaraldi, Giovanni
abstract

not available

2013 - L’evoluzione della terapia per il controllo dell’HIV.” Le comorbidità [Capitolo/Saggio]
Guaraldi, Giovanni; Garlassi, Elisa; A., Santoro
abstract

non disponibile

2013 - Life expectancy in the immune-recovery era: the evolving scenario of HIV epidemic in Northern Italy [Abstract in Rivista]
Guaraldi, Giovanni; Cossarizza, Andrea; C., Franceschi; A., Roverato; E., Vaccher; G., Tambussi; Garlassi, Elisa; Menozzi, Marianna; Mussini, Cristina; A., D’Arminio Monforte
abstract

National cohort and inter-cohort studies have been set to describe differences of Life Expectancy (LE) of HIV-infected individuals. the aim of this study was to assess the impact of immune-recovery on LE of HIV-patients undergoing cART.

2013 - Limited occurence of new grade 3-4 toxicity events with salvage regimens based on raltegravir and /or maraviroc: 96 weeks data from the ISS NIA cohort study [Abstract in Rivista]
Le, Weimer; M., Floridia; R., Bucciardini; S., Baroncelli; C. M., Galluzzo; M. F., Pirillo; V., Fragola; S., Donnini; M., Mirra; M., di Gregorio; S., Lucattini; L., Fucili; G., Angarano; N., Ladisa; A., Volpe; V., Vullo; G., D'Ettorre; G., Ceccarelli; M., Andreoni; L., Sarmati; D., Delle Rose; V., Tozzi; N., Petrosillo; R., Bellagamba; R., Libertone; S., Cicalini; L., Sighinolfi; D., Segala; O., Armignacco; R., Preziosi; C., Ferrari; A., Degli Antoni; A., Cavalli; G., Parruti; F., Sozio; L., Cosentino; A., Vivarelli; P. E., Manconi; F., Ort; M. L., Di Martino; P., Viale; G., Verrucchi; S., Tedeschi; M. S., Mura; M., Mannazzu; G., Cattari; M., Tavio; R., del Gobbo; A., Mataloni Paggi; A., Giacometti; O., Cirioni; E., Marchionni; C., Silvestri; S., Sebastianelli; L., Brescini; F., Baldelli; Guaraldi, Giovanni; Nardini, Giulia; Stentarelli, Chiara; Beghetto, Barbara
abstract

Limited occurence of new grade 3-4 toxicity events with salvage regimens based on raltegravir and /or maraviroc: 96 weeks data from the ISS NIA cohort study

2013 - Limited occurrence of new grade 3-4 toxicity events with salvage regimens based on raltegravir and /or maraviroc: 96 weeks data from the ISS NIA cohort study. [Abstract in Rivista]
L. E., Weimer; M., Floridia; R., Bucciardini; S., Baroncelli; C. M., Galluzzo; M. F., Pirillo; V., Fragola; S., Donnini; M., Mirra; M., Di Gragorio; S., Lucattini; L., Fucili; G., Angarano; N., Ladisa; A., Volpe; V., Vullo; G., D’Ettorre; G., Ceccarelli; M., Andreoni; L., Sarmati; D., Delle Rose; V., Tozzi; N., Petrosillo; R., Bellagamba; R., Libertone; S., Cicalini; L., Sighinolfi; D., Segala; O., Armignacco; R., Preziosi; C., Ferrari; A., Degli Antoni; A., Cavalli; G., Parruti; F., Sozio; L., Cosentino; A., Vivarelli; Pe, Manconi; F., Ort; Di Martino, M. L.; P., Viale; G., Verucchi; S., Tedeschi; Mura, M. S.; M., Mannazzu; G., Cattari; M., Tavio; R., Del Gobbo; A., Mataloni Paggi; A., Giacometti; O., Cirioni; E., Marchionni; C., Silvestri; S., Sebastianelli; L., Brescini; F., Baldelli; D., Francisci; E., Schiaroli; S., Bastianelli; Guaraldi, Giovanni; Nardini, Giulia; Stentarelli, Chiara; Beghetto, Barbara
abstract

Most of the available information on long-term toxicity of regimens based on raltegravir and/or maraviroc comes from controlled trials, and there is limited information on the occurrence and characteristics af adverse events in a setting of common clinical practice with frequent concomitant use of darunavir, enfuvirtide and etravirine. We anlyzed the number and characteristics of new adverse events grade 3-4 occurring in the first 96 weeks of treatment with salvage regimens based on raltegravir and /or maraviroc in an observational study.

2013 - MR quantitative biomarkers of non-alcoholic fatty liver disease: technical evolutions and future trends [Articolo su rivista]
Ligabue, Guido; Besutti, Giulia; Scaglioni, Riccardo; Stentarelli, Chiara; Guaraldi, Giovanni
abstract

Non-alcoholic fatty liver disease (NAFLD) is characterized by hepatic steatosis as the earliest manifestation and hallmark, and ranges from benign fatty liver to non-alcoholic steatohepatitis (NASH). Liver biopsy (LB) is considered the reference standard for NAFLD diagnosis, grading and characterization, but it is limited by its invasiveness and observer-dependence. Among imaging surrogates for the assessment of hepatic steatosis, MR is the most accurate. (1)H MR spectroscopy (MRS) provides a quantitative biomarker of liver fat content (LFC) called proton density fat fraction (PDFF), but it is time-consuming, not widely available and limited in sample size. Several MR imaging (MRI) techniques, in particular fat suppression and in-opposed phase techniques, have been used to quantify hepatic steatosis, mainly estimating LFC from water and fat signal intensities rather than proton densities. Several technical measures have been introduced to minimize the effect of confounding factors, in particular a low flip angle, a multiecho acquisition and a spectral modeling of fat with multipeak reconstruction to address respectively T1 effect, T2* effect, and the multifrequency interference effects of fat protons, allowing to use MRI to estimate LFC based on PDFF. Tang et al. evaluated MRI-estimated PDFF, obtained by applying the above-mentioned technical improvements, in the assessment of hepatic steatosis, using histopathology as the reference standard. The identification of PDFF thresholds, even though to be further explored and validated in larger and more diverse cohorts, is useful to identify steatosis categories based on MRI-based steatosis percentages. MRI, with the new refined techniques which provide a robust quantitative biomarker of hepatic steatosis (PDFF) evaluated on the whole liver parenchyma, is a promising non-invasive alternative to LB as the gold standard for steatosis diagnosis and quantification.

2013 - Multicenter Italian Experience in Liver Transplantation for Hepatocellular Carcinoma in HIV-Infected Patients [Articolo su rivista]
DI BENEDETTO, Fabrizio; Tarantino, Giuseppe; G., Ercolani; U., Baccarani; R., Montalti; N., De Ruvo; M., Berretta; G. L., Adani; M., Zanello; M., Tavio; Cautero, Nicola; U., Tirelli; Gerunda, Giorgio Enrico; Guaraldi, Giovanni; Pinna, Antonio Daniele
abstract

Abstract: Background. The aim of our work is to assess the clinical outcomes of liver transplantation (LT) for hepatocellular carcinoma (HCC) in HIV-coinfected patients. This is a multicenter study involving three Italian transplant centers in northern Italy: University of Modena, University of Bologna, and University of Udine. Patients and Methods. We compared 30 HIV-positive pants affected by HCC who underwent LT with 125 HIV-uninfected patients who received the same treatment from September 2004 to June 2009. At listing, there were no differences between HIV-infected and -uninfected patients regarding HCC features. Patients outside the University of California, San Francisco criteria (UCSF) were considered eligible for LT if a down-staging program permitted a reduction of tumor burden. Results. HIV-infected patients were younger, they were more frequently anti-HCV positive, and a higher number of HIV-infected patients presented a coinfection HBV-HCV. Pre-LT treatments (liver resection and or locoregional treatments) were similar between the two groups. Histological characteristics of the tumor were similar in patients with and without HIV infection. No differences were observed in terms of overall survival and HCC recurrence rates. Conclusion. LT for HCC is a feasible procedure and the presence of HIV does not particularly affect the post-LT outcome.

2013 - Non-AIDS defining cancers in the D:A:D Study - time trends and predictors of survival: A cohort study [Articolo su rivista]
Worm, S. W.; Bower, M.; Reiss, P.; Bonnet, F.; Law, M.; Fatkenheuer, G.; d'Arminio Monforte, A.; Abrams, D. I.; Grulich, A.; Fontas, E.; Kirk, O.; Furrer, H.; Wit, S. D.; Phillips, A.; Lundgren, J. D.; Sabin, C. A.; Butcher, D.; Delforge, M.; Fanti, I.; Franquet, X.; Geffard, S.; Gras, L.; Helweg-Larsen, J.; Hillebregt, M.; Kamara, D.; Kjaer, J.; Krum, E.; Mcmanus, H.; Meidahl, P.; Mocroft, A.; Nielsen, J.; Powderl, W.; Rickenbach, M.; Rode, R.; Ryom, L.; Salbol Brandt, R.; Schmidt Iversen, J.; Shortman, N.; Sjol, A.; Smith, C.; Torres, F.; Tverland, J.; Wright, S.; Zaheri, S.; de Wolf, F.; Smidt, J.; Ristola, M.; Katlama, C.; Viard, J-P.; Girard, P. -M.; Livrozet, J. M.; Vanhems, P.; Pradier, C.; Dabis, F.; Neau, D.; Rockstroh, J.; Schmidt, R.; Degen, O.; van Lunzen, J.; Stellbrink, H. J.; Staszewski, S.; Bogner, J.; Gargalianos, P.; Kosmidis, J.; Perdios, J.; Xylomenos, G.; Filandras, A.; Karabatsaki, E.; Panos, G.; Sambatakou, H.; Banhegyi, D.; Mulcahy, F.; Burke, M.; Turner, D.; Yust, I.; Hassoun, G.; Pollack, S.; Maayan, S.; Vella, S.; Esposito, R.; Mazeu, I.; Mussini, C.; Arici, C.; Pristera, R.; Gabbuti, A.; Mazzotta, F.; Lichtner, M.; Vullo, V.; Boer, K.; Geerlings, S. E.; Godfried, M. H.; Kuijpers, T. W.; Lange, J. M. A.; Nellen, F. J. B.; Pajkrt, D.; Prins, J. M.; Scherpbier, H. J.; Vrouenraets, S. M. E.; Wit, F. W. M. N.; van Vugt, M.; van der Meer, J. T. M.; van der Poll, T.; van der Valk, M.; Chirianni, A.; Gargiulo, M.; Montesarchio, E.; Antonucci, G.; Narciso, P.; Testa, A.; Vlassi, C.; Zaccarelli, M.; Castagna, A.; Gianotti, N.; Lazzarin, A.; Galli, M.; Ridolfo, A.; Rozentale, B.; Zeltina, I.; Chaplinskas, S.; Hemmer, R.; Staub, T.; Bruun, J.; Maeland, A.; Ormaasen, V.; Lowe, S.; Oude Lashof, A.; Schreij, G.; Gasiorowski, J.; Knysz, B.; Bakowska, E.; Horban, A.; Flisiak, R.; Grzeszczuk, A.; Boron-Kaczmarska, A.; Parczewski, M.; Pynka, M.; Beniowski, M.; Mularska, E.; Trocha, H.; Jablonowska, E.; Malolepsza, E.; Wojcik, K.; Antunes, F.; Caldeira, L.; Doroana, M.; Mansinho, K.; Maltez, F.; Bravenboer, B.; Pronk, M. J. H.; Duiculescu, D.; Rakhmanova, A.; Zakharova, N.; Buzunova, S.; Jevtovic, D.; Mokras, M.; Stanekova, D.; Tomazic, J.; Gonzalez-Lahoz, J.; Labarga, P.; Medrano, J.; Soriano, V.; Moreno, S.; Rodriguez, J. M.; Bravo, I.; Clotet, B.; Jou, A.; Paredes, R.; Puig, J.; Tural, C.; Gelinck, L. B. S.; Nouwen, J. L.; Rijnders, B. J. A.; Schurink, C. A. M.; Slobbe, L.; Verbon, A.; de Vries-Sluijs, T. E. M. S.; van der Ende, M. E.; van der Feltz, M.; Gatell, J. M.; Miro, J. M.; Domingo, P.; Gutierrez, M.; Mateo, G.; Sambeat, M. A.; Karlsson, A.; Flamholc, L.; Ledergerber, B.; Weber, J.; Cavassini, M.; Francioli, P.; Boffi, E.; Hirschel, B.; Battegay, M.; Elzi, L.; Chentsova, N.; Kravchenko, E.; Driessen, G. J. A.; Hartwig, N. G.; Frolov, V.; Kutsyna, G.; Servitskiy, S.; Krasnov, M.; Barton, S.; Johnson, A. M.; Mercey, D.; Johnson, M. A.; Murphy, M.; Scullard, G.; Fisher, M.; Leen, C.; Branger, J.; Akerlund, B.; Morfeldt, L.; Sundstro, m. A.; Thulin, G.; Koppel, K.; Hokangard, C.; Angarano, G.; Antinori, A.; Armignacco, O.; Castelli, F.; Cauda, R.; Di Perri, G.; Iardino, R.; Ippolito, G.; Moroni, M.; Perno, C. F.; Viale, P. L.; Von Schlosser, F.; Ammassari, A.; Andreoni, M.; Balotta, C.; Bonfanti, P.; Bonora, S.; Borderi, M.; Capobianchi, M. R.; Ceccherini-Silberstein, F.; Cinque, P.; Cozzi-Lepri, A.; De Luca, A.; Gervasoni, C.; Girardi, E.; Gori, A.; Guaraldi, G.; Lo Caputo, S.; Madeddu, G.; Maggiolo, F.; Marchetti, G.; Marcotullio, S.; Monno, L.; Murri, R.; Puoti, M.; Torti, C.; Cicconi, P.; Formenti, T.; Galli, L.; Lorenzini, P.; Costantini, A.; Giacometti, A.; Riva, A.; Carrisa, C.; Lazzari, G.; Verucchi, G.; Kauffmann, R. H.; Minardi, C.; Abeli, C.; Quirino, T.; Manconi, P. E.; Piano, P.; Falasca, K.; Vecchiet, J.; Segala, D.; Sighinolfi, L.; Alessandrini, A.; Cassola, G.; Mazzarello, G.; Piscopo, R.; Viscoli, G.; Belvisi, V.; Mastroianni, C.; Caramma, I.; Castelli, P.; Chiodera, A.; Alleman, M. A.; Bouwhuis
abstract

Background: Non-AIDS defining cancers (NADC) are an important cause of morbidity and mortality in HIV-positive individuals. Using data from a large international cohort of HIV-positive individuals, we described the incidence of NADC from 2004-2010, and described subsequent mortality and predictors of these.Methods: Individuals were followed from 1st January 2004/enrolment in study, until the earliest of a new NADC, 1st February 2010, death or six months after the patient's last visit. Incidence rates were estimated for each year of follow-up, overall and stratified by gender, age and mode of HIV acquisition. Cumulative risk of mortality following NADC diagnosis was summarised using Kaplan-Meier methods, with follow-up for these analyses from the date of NADC diagnosis until the patient's death, 1st February 2010 or 6&nbsp;months after the patient's last visit. Factors associated with mortality following NADC diagnosis were identified using multivariable Cox proportional hazards regression.Results: Over 176,775 person-years (PY), 880 (2.1%) patients developed a new NADC (incidence: 4.98/1000PY [95% confidence interval 4.65, 5.31]). Over a third of these patients (327, 37.2%) had died by 1st February 2010. Time trends for lung cancer, anal cancer and Hodgkin's lymphoma were broadly consistent. Kaplan-Meier cumulative mortality estimates at 1, 3 and 5&nbsp;years after NADC diagnosis were 28.2% [95% CI 25.1-31.2], 42.0% [38.2-45.8] and 47.3% [42.4-52.2], respectively. Significant predictors of poorer survival after diagnosis of NADC were lung cancer (compared to other cancer types), male gender, non-white ethnicity, and smoking status. Later year of diagnosis and higher CD4 count at NADC diagnosis were associated with improved survival. The incidence of NADC remained stable over the period 2004-2010 in this large observational cohort.Conclusions: The prognosis after diagnosis of NADC, in particular lung cancer and disseminated cancer, is poor but has improved somewhat over time. Modifiable risk factors, such as smoking and low CD4 counts, were associated with mortality following a diagnosis of NADC. © 2013 Worm et al.; licensee BioMed Central Ltd.

2013 - Predictive Accuracy of VACS Index for all cause Mortality in HIV-infected People enrolled in a large cohort in Italy [Abstract in Atti di Convegno]
Gazzola, L; Guaraldi, Giovanni; De Luca, A; Antinori, A; Nicastri, E; Castagna, A; Di Perri, G; Pellizzer, G; Angarano, G; Viale, P; Cozzi Lepri, A; d'Arminio Monforte, A. .
abstract

Objective: To determine the Accuracy of VACS index to predict 5-years all-cause mortality and to compare it with thet of other prognostic indices in the ICONA cohort. Conclusion: The VACS index mortality risk demonstrated a very good predictive accuracy in cART-treated HIV infected patients seen for care in Italy, overall and in specific subgroups under-represented in cohorts used to derive and previously validate the index. Overall its predictive value was similar to other more parsimonious indices. Late presentation of HIV and virological response to cART were independent predictors of having a high VACS score.

2013 - Pregnancy Outcomes in HIV-Infected Women of Advanced Maternal Age [Articolo su rivista]
Giuseppina, Liuzzi; Carmela, Pinnetti; Marco, Floridia; Enrica, Tamburrini; Giulia, Masuelli; Serena, Dalzero; Matilde, Sansone; Vania, Giacomet; Anna Maria Degli, Antoni; Guaraldi, Giovanni; Alessandra, Meloni; Anna, Maccabruni; Salvatore, Alberico; Vincenzo, Portelli; Marina, Ravizza
abstract

BACKGROUND: There is limited information on pregnancy outcomes in women with HIV who are of a more advanced maternal age. METHODS: Data from a national observational study in Italy were used to evaluate the risk of nonelective cesarean section, preterm delivery, low birthweight, major birth defects, and small gestational age-adjusted birthweight according to maternal age (<35 and ≥35 years, respectively). RESULTS: Among 1,375 pregnancies with live births, 82.4% of deliveries were elective cesarean sections, 15.8% were nonelective cesarean sections, and 1.8% were vaginal deliveries. Rates of nonelective cesarean section were similar among mothers ≥35 and <35 years (odds ratio [OR], 1.22; 95% CI, 0.90-1.65;P = .19). Preterm delivery and low birthweight were significantly more common among women ≥35 years in univariate but not in multivariate analyses. Newborns from women ≥35 and <35 years showed no differences inZ scores of birthweight, with a similar occurrence of birthweight <10th percentile (12.1% vs 12.0%; OR, 1.02; 95% CI, 0.71-1.46;P = .93). The overall rate of birth defects was 3.4% (95% CI, 2.4-4.4), with no differences by maternal age (≥35 years, 3.5%; <35 years, 3.3%; OR, 1.05; 95% CI, 0.56-1.98;P = .88). DISCUSSION: In this study of pregnant women with HIV, older women were at higher risk of some adverse pregnancy outcomes, such as preterm delivery and low birthweight. The association, however, did not persist in multivariable analyses, suggesting a role of some predisposing factors associated with older age.

2013 - Prevalence and predictors of preclinical coronary heart disease in post-menopause period [Abstract in Rivista]
Guaraldi, Giovanni; Zona, Stefano; Besutti, Giulia; Scaglioni, Riccardo; Stentarelli, Chiara; Menozzi, Marianna; Garlassi, Elisa; Ligabue, Guido; Mussini, Cristina; P., Raggi
abstract

There are very few longitudinal studies of change in coronary artery calcium (CAC) across the menopause period, when it is expected there would be a significant increase in coronary heart disease. CAC>0 identifies preclinical coronary artery disease. We aimed to evaluate risk factors for detectable CAC among HIV-infected women across the menopause period.

2013 - Randomized Trial to Evaluate Cardiometabolic and Endothelial Function in Patients with Plasma HIV-1 RNA Suppression Switching to Darunavir/Ritonavir with or without Nucleoside Analogues [Articolo su rivista]
Guaraldi, Giovanni; Zona, Stefano; Cossarizza, Andrea; L., Vernacotola; Carli, Federica; A., Lattanzi; Beghetto, Barbara; Orlando, Gabriella; DE BIASI, Sara; R., Termini; M., Garau
abstract

Background: We performed a study to evaluate change in cardiometabolic and endothelial function in HIV-infected patients switching to darunavir/ritonavir (DRV/r) monotherapy versus triple therapy. Methods: The MONARCH trial recruited 30 patients who were taking triple combination therapy and with HIV RNA<40 copies/ mL. Patients were randomized to either DRV/r 800/100 mg once daily (OD) monotherapy or DRV/r 800/100 mg OD plus 2 nucleoside reverse transcriptase inhibitors (NRTIs). The primary objective was to assess endothelial function change from baseline to 24 and 48 weeks in brachial artery flow-mediated dilation (FMD) test; changes in endothelial precursor cells (EPCs) and circulating endothelial cells (CECs) were secondary objectives. Results: At baseline, the median age of participants was 43 years, 77% were men, and median CD4 cell count was 585 cells/μL. The median FMD (%) decreased in both arms in the study period (P ≯ .05), with no statistically significant difference between arms (10.7% at baseline and 6.7% at week 48 in the DRV/r + 2 NRTIs arm; 11.1% at baseline and 8.8% at week 48 in the DRV/r arm). The changes at week 48 were similar in the 2 arms for EPCs and CECs. Total cholesterol and low-density lipoprotein (LDL) cholesterol showed larger rises to week 48 in the DRV/r arm monotherapy group than in the triple-therapy group (+26 vs +9 mg/dL for total cholesterol and +14 vs +5 mg/dL for LDL cholesterol). Conclusions: In the MONARCH trial, switching from triple combination treatment to DRV/r, with or without nucleoside analogues, did not translate into clinically meaningful reductions in endothelial function as measured by FMD.

2013 - Response to raltegravir-based salvage therapy in HIV-infected patients with hepatitis C virus or hepatitis B virus coinfection [Articolo su rivista]
L. E., Weimer; V., Fragola; M., Floridia; Guaraldi, Giovanni; N., Ladisa; D., Francisci; R., Bellagamba; A., Degli Antoni; G., Parruti; A., Giacometti; P. E., Manconi; A., Vivarelli; G., D'Ettorre; M. S., Mura; S., Cicalini; R., Preziosi; L., Sighinolfi; G., Verucchi; R., Libertone; M., Tavio; L., Sarmati; R., Bucciardini
abstract

OBJECTIVES: To define the impact of coinfection with hepatitis B virus (HBV) or hepatitis C virus (HCV) on viroimmunological response to raltegravir-based salvage regimens that also include new HIV inhibitors such as maraviroc, darunavir and etravirine. METHODS: We used data from a national observational study of patients starting raltegravir-based regimens to compare virological suppression and CD4 cell change from baseline in patients with and without concomitant HBV or HCV infection. RESULTS: Overall, 275 patients (107 coinfected and 168 non-coinfected) were evaluated. Coinfected patients were more commonly former intravenous drug users and had a longer history of HIV infection and higher baseline aminotransferase levels. Both HIV-RNA and CD4 response were similar in the two groups. Mean time to first HIV-RNA copy number &lt;50 copies/mL was 4.1 months (95% CI 3.5-4.6) in non-coinfected patients and 3.9 months (95% CI 3.3-4.5) in coinfected patients (hazard ratio 1.039, 95% CI 0.761-1.418, P = 0.766, log-rank test). The risk of developing new grade 3-4 hepatic adverse events was significantly higher in coinfected patients (hazard ratio 1.779, 95% CI 1.123-2.817, P = 0.009). The two groups of coinfected and non-coinfected patients had similar rates of interruption of any baseline drug (hazard ratio 1.075, 95% CI 0.649-1.781, P = 0.776) and of raltegravir (hazard ratio 1.520, 95% CI 0.671-3.447, P = 0.311). Few AIDS-defining events and deaths occurred. CONCLUSIONS: Viroimmunological response to regimens based on raltegravir and other recent anti-HIV inhibitors is not negatively affected by coinfection with HBV or HCV. Liver toxicity, either pre-existing or new, is more common in coinfected patients, but with no increased risk of treatment interruption.

2013 - TB meningitis in HIV-positive patients in Europe and Argentina: Clinical dutcome and factors associated with mortality [Articolo su rivista]
Efsen, A. M. W.; Panteleev, A. M.; Grint, D.; Podlekareva, D. N.; Vassilenko, A.; Rakhmanova, A.; Zeltina, I.; Losso, M. H.; Miller, R. F.; Girardi, E.; Cayla, J.; Post, F. A.; Miro, J. M.; Bruyand, M.; Furrer, H.; Obel, N.; Lundgren, J. D.; Mocroft, A.; Kirk, O.; Toibaro, J. J.; Warley, E.; Tamayo, N.; Cristina Ortiz, M.; Scapelatto, P.; Bottaro, E.; Murano, F.; Miachans, M.; Contarelli, J.; Massera, L.; Corral, J.; Hualde, M.; Miglioranza, C.; Corti, M.; Metta, H.; Casiro, A.; Cuini, R.; Laplume, H.; David, D.; Marson, C.; Lupo, S.; Trape, L.; Garcia Messina, O.; Gear, O.; Bruguera, J. M.; Karpov, I.; Skrahina, E.; Skrahin, A.; Zhavoronok, S.; Mitsura, V.; Ruzanov, D.; Bondarenko, V.; Suetnov, O.; Paduto, D.; Gerstoft, J.; Kronborg, G.; Pedersen, C.; Larsen, C. S.; Pedersen, G.; Laursen, A. L.; Nielsen, L.; Jensen, J.; Dabis, F.; Chene, G.; Lawson-Ayayi, S.; Thiebaut, R.; Wittkop, L.; Morlat, P.; Bonnet, F.; Bernard, N.; Hessamfar, M.; Lacoste, D.; Vandenhende, M. A.; Dupon, M.; Dauchy, F. A.; Dutronc, H.; Longy-Boursier, M.; Mercie, P.; Duffau, P.; Roger Schmeltz, J.; Malvy, D.; Pistone, T.; Receveur, M. C.; Neau, D.; Cazanave, C.; Ochoa, A.; Vareil, M. O.; Pellegrin, J. L.; Viallard, J. F.; Greib, C.; Lazaro, E.; Fleury, H.; Lafon, M. E.; Reigadas, S.; Trimoulet, P.; Breilh, D.; Molimard, M.; Bouchet, S.; Titier, K.; Moreau, J. F.; Pellegrin, I.; Haramburu, F.; Arcachon, G.; Dupont, A.; Gerard, Y.; Caunegre, L.; Andre, K.; Bonnal, F.; Farbos, S.; Gemain, M. C.; Ceccaldi, J.; Tchamgoue, S.; De Witte, S.; Courtault, K.; Monlun, E.; Gaborieau, V.; Lataste, P.; Meraud, J. P.; Chossat, I.; Carvalho, A. C.; Basche, R.; Hamad, I. E.; Ricci, B. A.; Maggiolo, F.; Ravasio, V.; Mussini, C.; Prati, F.; Castelletti, S.; Ammassari, A.; Antinori, A.; Bellagamba, R.; Busi Rizzi, E.; Cicalini, S.; Corpolongo, A.; Capaldo, A.; Di Caro, A.; Goletti, D.; Grisetti, S.; Gualano, G.; Lauria, F. N.; Parracino, L.; Palmieri, F.; Petrosillo, N.; Pinetti, C.; Sampaolesi, A.; Moroni, M.; Angarano, G.; Armignacco, O.; d'Arminio Monforte, A.; Castelli, F.; Cauda, R.; Di Perri, G.; Galli, M.; Iardino, R.; Ippolito, G.; Lazzarin, A.; Perno, C. F.; von Schloesser, F.; Viale, P.; Castagna, A.; Ceccherini-Silberstein, F.; Cozzi-Lepri, A.; Lo Caputo, S.; Puoti, M.; Andreoni, M.; Balotta, C.; Bonfanti, P.; Bonora, S.; Borderi, M.; Capobianchi, M. R.; Cingolani, A.; Cinque, P.; De Luca, A.; Di Biagio, A.; Gianotti, N.; Gori, A.; Guaraldi, G.; Lapadula, G.; Lichtner, M.; Madeddu, G.; Marchetti, G.; Marcotullio, S.; Monno, L.; Quiros Roldan, E.; Rusconi, S.; Cicconi, P.; Fanti, I.; Formenti, T.; Galli, L.; Lorenzini, P.; Giacometti, A.; Costantini, A.; Carrisa, C.; Suardi, C.; Vanino, E.; Verucchi, G.; Minardi, C.; Quirino, T.; Abeli, C.; Manconi, P. E.; Piano, P.; Vecchiet, J.; Falasca, K.; Sighinolfi, L.; Segala, D.; Mazzotta, F.; Cassola, G.; Viscoli, G.; Alessandrini, A.; Piscopo, R.; Mazzarello, G.; Mastroianni, C.; Belvisi, V.; Caramma, I.; Castelli, A. P.; Rizzardini, G.; Ridolfo, A. L.; Piolini, R.; Salpietro, S.; Carenzi, L.; Moioli, M. C.; Puzzolante, C.; Abrescia, N.; Chirianni, A.; Guida, M. G.; Gargiulo, M.; Baldelli, F.; Francisci, D.; Parruti, G.; Ursini, T.; Magnani, G.; Ursitti, M. A.; Vullo, V.; D'Avino, A.; Gallo, L.; Nicastri, E.; Acinapura, R.; Capozzi, M.; Libertone, R.; Tebano, G.; Cattelan, A.; Mura, M. S.; Caramello, P.; Orofino, G. C.; Sciandra, M.; Pellizzer, G.; Manfrin, V.; Riekstina, V.; Aldins, P.; Duiculescu, D.; Malashenkov, E.; Kozlov, A.; Buzunova, S.; Garcia-Goez, J. F.; Moreno Camacho, A.; Martinez, J. A.; Gonzalez, J.; Garcia-Alcaide, F.; de Lazzari, E.; Gatell, J. M.; Sanchez, P.; Lopezcolomes, J. L.; Martinez-Lacasa, X.; Falco, V.; Imaz, A.; Ocana, I.; Vidal, R.; Sambeat, M. A.; Moreno-Martinez, A.; Orcau, A.; Weber, R.; Battegay, M.; Hirschel, B.; Cavassini, M.; Bernasconi, E.; Schmid, P.; Rickenbach, M.; Campbell, L.; Arenas-Pinto, A.; Chentsova, N.; Kjaer, J.
abstract

Objectives. The study aimed at describing characteristics and outcome of tuberculous meningitis (TBM) in HIV-positive patients and comparing these parameters with those of extrapulmonary TB (TBEP) and pulmonary TB (TBP). Methods. Kaplan-Meier estimation and Poisson regression models were used to assess the mortality following TB diagnosis and to evaluate potential prognostic factors for the 3 groups of TB patients separately. Results. A total of 100 patients with TBM, 601 with TBEP, and 371 TBP were included. Patients with TBM had lower CD4 cell counts and only 17.0% received antiretroviral therapy (ART) at TB diagnosis. The cumulative probability of death at 12 months following TB was 51.2% for TBM (95% CI 41.4-61.6%), 12.3% for TBP (8.9-15.7%), and 19.4% for TBEP (16.1-22.6) (P &lt; 0.0001; log-rank test). For TBM, factors associated with a poorer prognosis were not being on ART (adjusted incidence rate ratio (aIRR) 4.00 (1.72-9.09), a prior AIDS diagnosis (aIRR = 4.82 (2.61-8.92)), and receiving care in Eastern Europe (aIRR = 5.41 (2.58-11.34))). Conclusions. TBM among HIV-positive patients was associated with a high mortality rate, especially for patients from Eastern Europe and patients with advanced HIV-infection, which urgently calls for public health interventions to improve both TB and HIV aspects of patient management. © 2013 Anne Marie W. Efsen et al.

2013 - Tesamorelin for the treatment of excess abdominal fat in HIV-infected individuals with lipodistrophy [Articolo su rivista]
Guaraldi, Giovanni; Stentarelli, Chiara
abstract

Metabolic and morphologic abnormalities in persons with HIV remain common contributors to stigma and morbidity. Increased abdominal circumference and visceral adiposity were first recognized in the late 1990s, soon after the advent of effective combination antiretroviral therapy. Visceral adiposity is commonly associated with metabolic abnormalities including low HDL- cholesterol, raised triglycerides, insulin resistance and hypertension, a constellation of risk factors for cardiovascular disease and diabetes mellitus known as the metabolic syndrome. Medline and conference abstracts were searched to identify clinical research on factors associated with visceral adiposity and randomized studies of management approaches. Data were critically reviewed by physicians familiar with the field. A range of host and lifestyle factors, as well as antiretroviral drug choice, were associated with increased visceral adiposity. Management approaches included treatment switching. Supraphysiological doses of recombinant HGH and the hGHRH tesamorelin both significantly and selectively reduce visceral fat over 12-24 weeks; however, the benefits are only maintained if dosing is continued. In summary, the prevention and management of visceral adiposity remains a substantial challenge in clinical practice.

2013 - Urolitiasi in corso di infezione da HIV: revisione della letteratura. [Articolo su rivista]
Guaraldi, Giovanni; Dolci, Giovanni; Bellasi, Antonio
abstract

L'eccesso di pazienti in condizioni dismetaboliche trattati con ATV/r può rappresentare un challenging bias che comporta un maggior rischio di urolitiasi.

2012 - A randomized, pilot trial to evaluate glomerular filtration rate by creatinine or cystatin C in naïve HIV-infected patients after tenofovir/emtricitabine in combination with atazanavir/ritonavir or efavirenz. [Articolo su rivista]
L., Albini; B. M., Cesana; D., Motta; E., Focà; D., Gotti; A., Calabresi; I., Izzo; R., Bellagamba; R., Fezza; P., Narciso; L., Sighinolfi; P., Maggi; E., Quiros Roldan; L., Manili; Guaraldi, Giovanni; G., Lapadula; C., Torti
abstract

BACKGROUND: Glomerular filtration rate (GFR) estimated by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation based on creatinine or cystatine C may be more accurate methods especially in patients without chronic kidney disease. There is lack of data on GFR estimated by these methods in patients on HAART.METHODS: Antiretroviral-naïve HIV-infected patients were randomized to TDF/emtricitabine (FTC) in association with ATV/r or EFV. Patients had to have an actual creatinine clearance &gt;50 ml/min (24 hour urine collection) and were followed for 48 weeks.RESULTS: Ninety-one patients (48 ATV/r, 43 EFV) were recruited. Using the CKD-EPI creatinine formula, there was a significant decrease in GFR up to week 48 in patients receiving ATV/r (4.9 mL/min/m; P =0.02) compared to a not statistically significant increment in patients prescribed EFV. Using the cystatin C-based equation, we found greater decrease in GFR in both arms, although, in the EFV arm, the decrease was not statistically significant (5.8 mL/min/m, P=0.92). At multivariable analysis, ATV/r was a significant predictor of greater decrease in eGFR (P=0.0046) only with CKD-EPI creatinine.CONCLUSIONS: ATV/r plus TDF caused greater GFR decreases compared to EFV. The evaluation of eGFR by cystatin C confirmed this result but this method appeared to be more stringent, probably precluding the possibility to detect a significant difference in the pattern of eGFR evolution between the two arms over time. More studies are needed to understand the clinical relevance of these alterations and whether cystatin C is a more appropriate method for monitoring GFR in clinical practice.

2012 - Abacavir and Tenofovir impact on endothelial. [Abstract in Rivista]
Guaraldi, Giovanni; Zona, Stefano; Roverato, A; Orlando, Gabriella; Carli, Federica; Lattanzi, A; Manzini, L; Bisi, L; Cicognani, A; Rossi, Rosario
abstract

Flow mediated dilation (FMD) of the brachial artery is an endothelial function test, that has been used to assess the impact of cardiovascular induced drug toxicity. The objective of the study was to analyse the impact of abacavir and tenofovir on endothelial function.

2012 - Adverse Outcome Analyses of Observational Data: Assessing Cardiovascular Risk in HIV Disease. [Articolo su rivista]
V. A., Triant; F., Josephson; C. G., Rochester; K. N., Althoff; K., Marcus; R., Munk; C., Cooper; R. B., D'Agostino; D., Costagliola; C. A., Sabin; P. L., Williams; S., Hughes; W. S., Post; N., Chandra Strobos; Guaraldi, Giovanni; S. S., Young; R., Obenchain; R., Bedimo; V., Miller; J., Strobos
abstract