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Monica ZACCARELLI

Personale tecnico amministrativo
Dipartimento di Ingegneria "Enzo Ferrari"

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Pubblicazioni

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 > 12 or 24 weeks after stopping treatment. Results: Numbers and percentages for the stages of the HCV continuum of care were as follows: anti-HCV positive (n = 5173), HCV RNA tested (4207 of 5173; 81.3%), currently HCV RNA positive (3179 of 5173; 61.5%), ever HCV RNA positive (n = 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 < 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.

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 - 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 < 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 < 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 < 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 < 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 - Incidence of cancer and overall risk of mortality in individuals treated with raltegravir-based and non-raltegravir-based combination antiretroviral therapy regimens [Articolo su rivista]
Cozzi-Lepri, A.; Zangerle, R.; Machala, L.; Zilmer, K.; Ristola, M.; Pradier, C.; Kirk, O.; Sambatakou, H.; Fatkenheuer, G.; Yust, I.; Schmid, P.; Gottfredsson, M.; Khromova, I.; Jilich, D.; Flisiak, R.; Smidt, J.; Rozentale, B.; Radoi, R.; Losso, M. H.; Lundgren, J. D.; Mocroft, A.; Kundro, M.; Schmied, B.; Karpov, I.; Vassilenko, A.; Mitsura, V. M.; Paduto, D.; Clumeck, N.; De Wit, S.; Delforge, M.; Florence, E.; Vandekerckhove, L.; Hadziosmanovic, V.; Begovac, J.; Sedlacek, D.; Kronborg, G.; Benfield, T.; Gerstoft, J.; Katzenstein, T.; Moller, N. F.; Pedersen, C.; Ostergaard, L.; Wiese, L.; Nielsen, L. N.; Aho, I.; Viard, J. -P.; Girard, P. -M.; Fontas, E.; Duvivier, C.; Rockstroh, J.; Schmidt, R.; Degen, O.; Stellbrink, H. J.; Stefan, C.; Bogner, J.; Chkhartishvili, N.; Gargalianos, P.; Xylomenos, G.; Lourida, P.; Szlavik, J.; Mulcahy, F.; Turner, D.; Burke, M.; Shahar, E.; Hassoun, G.; Elinav, H.; Haouzi, M.; Elbirt, D.; Sthoeger, Z. M.; D'Arminio Monforte, A.; 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.; Uzdaviniene, V.; Matulionyte, R.; Staub, T.; Hemmer, R.; Reiss, P.; Ormaasen, V.; Maeland, A.; Bruun, J.; Knysz, B.; Gasiorowski, J.; Inglot, M.; Horban, A.; Bakowska, E.; Grzeszczuk, A.; Parczewski, M.; Maciejewska, K.; Aksak-Was, B.; Beniowski, M.; Mularska, E.; Smiatacz, T.; Gensing, M.; Jablonowska, E.; Malolepsza, E.; Wojcik, K.; Mozer-Lisewska, I.; Caldeira, L.; Mansinho, K.; Maltez, F.; Oprea, C.; Panteleev, A.; Panteleev, O.; Yakovlev, A.; Trofimora, T.; Kuzovatova, E.; Borodulina, E.; Vdoushkina, E.; Jevtovic, D.; Tomazic, J.; Gatell, J. M.; Miro, J. M.; Moreno, S.; Rodriguez, J. M.; Clotet, B.; 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.; Scherrer, A.; Weber, R.; Cavassini, M.; Calmy, A.; Furrer, H.; Battegay, M.; Kuznetsova, A.; Kyselyova, G.; Sluzhynska, M.; Gazzard, B.; Johnson, A. M.; Simons, E.; Edwards, S.; Phillips, A.; Johnson, M. A.; Orkin, C.; Weber, J.; Scullard, G.; Clarke, A.; Leen, C.; Thiebaut, R.; Burger, D.; Peters, L.; Matthews, C.; Fischer, A. H.; Bojesen, A.; Raben, D.; Kristensen, D.; Gronborg Laut, K.; Larsen, J. F.; Podlekareva, D.; Shepherd, L.; Schultze, A.; Amele, S.
abstract

Objectives: There are currently few data on the long-term risk of cancer and death in individuals taking raltegravir (RAL). The aim of this analysis was to evaluate whether there is evidence for an association. Methods: The EuroSIDA cohort was divided into three groups: those starting RAL-based combination antiretroviral therapy (cART) on or after 21 December 2007 (RAL); a historical cohort (HIST) of individuals adding a new antiretroviral (ARV) drug (not RAL) to their cART between 1 January 2005 and 20 December 2007, and a concurrent cohort (CONC) of individuals adding a new ARV drug (not RAL) to their cART on or after 21 December 2007. Baseline characteristics were compared using logistic regression. The incidences of newly diagnosed malignancies and death were compared using Poisson regression. Results: The RAL cohort included 1470 individuals [with 4058 person-years of follow-up (PYFU)] compared with 3787 (4472 PYFU) and 4467 (10 691 PYFU) in the HIST and CONC cohorts, respectively. The prevalence of non-AIDS-related malignancies prior to baseline tended to be higher in the RAL cohort vs. the HIST cohort [adjusted odds ratio (aOR) 1.31; 95% confidence interval (CI) 0.95–1.80] and vs. the CONC cohort (aOR 1.89; 95% CI 1.37–2.61). In intention-to-treat (ITT) analysis (events: RAL, 50; HIST, 45; CONC, 127), the incidence of all new malignancies was 1.11 (95% CI 0.84–1.46) per 100 PYFU in the RAL cohort vs. 1.20 (95% CI 0.90–1.61) and 0.83 (95% CI 0.70–0.99) in the HIST and CONC cohorts, respectively. After adjustment, there was no evidence for a difference in the risk of malignancies [adjusted rate ratio (RR) 0.73; 95% CI 0.47–1.14 for RALvs. HIST; RR 0.95; 95% CI 0.65–1.39 for RALvs. CONC] or mortality (adjusted RR 0.87; 95% CI 0.53–1.43 for RALvs. HIST; RR 1.14; 95% CI 0.76–1.72 for RALvs. CONC). Conclusions: We found no evidence for an oncogenic risk or poorer survival associated with using RAL compared with control groups.

2018 - Long-term effectiveness of recommended boosted protease inhibitor-based antiretroviral therapy in Europe [Articolo su rivista]
Santos, J. R.; Cozzi-Lepri, A.; Phillips, A.; De Wit, S.; Pedersen, C.; Reiss, P.; Blaxhult, A.; Lazzarin, A.; Sluzhynska, M.; Orkin, C.; Duvivier, C.; Bogner, J.; Gargalianos-Kakolyris, P.; Schmid, P.; Hassoun, G.; Khromova, I.; Beniowski, M.; Hadziosmanovic, V.; Sedlacek, D.; Paredes, R.; Lundgren, J. D.; Losso, M.; Kundro, M.; Schmied, B.; Zangerle, R.; Karpov, I.; Vassilenko, A.; Mitsura, V. M.; Paduto, D.; Clumeck, N.; Delforge, M.; Florence, E.; Vandekerckhove, L.; Begovac, J.; Machala, L.; Jilich, D.; Kronborg, G.; Benfield, T.; Gerstoft, J.; Katzenstein, T.; Moller, N. F.; Ostergaard, L.; Wiese, L.; Nielsen, L. N.; Zilmer, K.; Smidt, J.; Ristola, M.; Aho, I.; Viard, J. -P.; Girard, P. -M.; Pradier, C.; Fontas, E.; Rockstroh, J.; Schmidt, R.; Degen, O.; Stellbrink, H. J.; Stefan, C.; Fatkenheuer, G.; Chkhartishvili, N.; Gargalianos, P.; Xylomenos, G.; Lourida, P.; Sambatakou, H.; Szlavik, J.; Gottfredsson, M.; Mulcahy, F.; Yust, I.; Turner, D.; Burke, M.; Shahar, E.; Elinav, H.; Haouzi, M.; Elbirt, D.; Sthoeger, Z. M.; D'Arminio Monforte, A.; Esposito, R.; Mazeu, I.; Mussini, C.; Mazzotta, F.; Gabbuti, A.; Vullo, V.; Lichtner, M.; Zaccarelli, M.; Antinori, A.; Acinapura, R.; Plazzi, M.; Castagna, A.; Gianotti, N.; Galli, M.; Ridolfo, A.; Rozentale, B.; Uzdaviniene, V.; Matulionyte, R.; Staub, T.; Hemmer, R.; Ormaasen, V.; Maeland, A.; Bruun, J.; Knysz, B.; Gasiorowski, J.; Inglot, M.; Horban, A.; Bakowska, E.; Flisiak, R.; Grzeszczuk, A.; Parczewski, M.; Pynka, M.; Maciejewska, K.; Mularska, E.; Smiatacz, T.; Gensing, M.; Jablonowska, E.; Malolepsza, E.; Wojcik, K.; Mozer-Lisewska, I.; Caldeira, L.; Mansinho, K.; Maltez, F.; Radoi, R.; Panteleev, A.; Panteleev, O.; Yakovlev, A.; Trofimora, T.; Kuzovatova, E.; Borodulina, E.; Vdoushkina, E.; Jevtovic, D.; Tomazic, J.; Gatell, J. M.; Miro, J. M.; Moreno, S.; Rodriguez, J. M.; Clotet, B.; Jou, A.; Tural, C.; Puig, J.; Bravo, I.; Domingo, P.; Gutierrez, M.; Mateo, G.; Sambeat, M. A.; Laporte, J. M.; Falconer, K.; Thalme, A.; Sonnerborg, A.; Flamholc, L.; Scherrer, A.; Weber, R.; Cavassini, M.; Calmy, A.; Furrer, H.; Battegay, M.; Kuznetsova, A.; Kyselyova, G.; Gazzard, B.; Johnson, A. M.; Simons, E.; Edwards, S.; Johnson, M. A.; Mocroft, A.; Weber, J.; Scullard, G.; Clarke, A.; Leen, C.; Gatell, J.; Ledergerber, B.; Kirk, O.; Peters, L.; Matthews, C.; Fischer, A. H.; Bojesen, A.; Raben, D.; Kristensen, D.; Gronborg Laut, K.; Larsen, J. F.; Podlekareva, D.; Shepherd, L.; Schultze, A.; Thiebaut, R.; Burger, D.
abstract

Objectives: The aim of the study was to evaluate the long-term response to antiretroviral treatment (ART) based on atazanavir/ritonavir (ATZ/r)-, darunavir/ritonavir (DRV/r)-, and lopinavir/ritonavir (LPV/r)-containing regimens. Methods: Data were analysed for 5678 EuroSIDA-enrolled patients starting a DRV/r-, ATZ/r- or LPV/r-containing regimen between 1 January 2000 and 30 June 2013. Separate analyses were performed for the following subgroups of patients: (1) ART-naïve subjects (8%) at ritonavir-boosted protease inhibitor (PI/r) initiation; (2) ART-experienced individuals (44%) initiating the new PI/r with a viral load (VL) ≤500 HIV-1 RNA copies/mL; and (3) ART-experienced patients (48%) initiating the new PI/r with a VL >500 copies/mL. Virological failure (VF) was defined as two consecutive VL measurements >200 copies/mL ≥24 weeks after PI/r initiation. Kaplan–Meier and multivariable Cox models were used to compare risks of failure by PI/r-based regimen. The main analysis was performed with intention-to-treat (ITT) ignoring treatment switches. Results: The time to VF favoured DRV/r over ATZ/r, and both were superior to LPV/r (log-rank test; P < 0.02) in all analyses. Nevertheless, the risk of VF in ART-naïve patients was similar regardless of the PI/r initiated after controlling for potential confounders. The risk of VF in both treatment-experienced groups was lower for DRV/r than for ATZ/r, which, in turn, was lower than for LPV/r-based ART. Conclusions: Although confounding by indication and calendar year cannot be completely ruled out, in ART-experienced subjects the long-term effectiveness of DRV/r-containing regimens appears to be greater than that of ATZ/r and LPV/r.

2018 - Long-term efficacy of dolutegravir in treatment-experienced subjects failing therapy with HIV-1 integrase strand inhibitor-resistant virus [Articolo su rivista]
Castagna, A.; Ferrara, M.; Galli, L.; Comi, L.; Sterrantino, G.; Cenderello, G.; Zaccarelli, M.; Foca, E.; Roncadori, A.; Lazzarin, A.; Chichino, G.; Mantia, E.; Butini, L.; Costantini, A.; Giacometti, A.; Tavio, M.; Grassini, M.; Valle, M.; Vaccher, E.; Martellotta, F.; Schioppa, O.; Maggiolo, F.; Viale, P.; Borderi, M.; Calza, L.; Moratello, L.; Magistrelli, E.; Castelli, F.; Festa, E.; Quirino, T.; Campus, M.; Businco, F.; Celesia, B. M.; La Rosa, R.; Pan, A.; Fornabaio, C.; Mazzotta, F.; Di Pietro, M.; Bartoloni, A.; Ferrara, S.; Mastroianni, A.; Di Cesare, S.; Viscoli, C.; Di Biagio, A.; Cassola, G.; Penco, G.; Cericola, A.; Nencioni, C.; Carli, T.; Vigano, P.; Re, T.; Del Fiorentino, A.; Gattuso, G.; Palvarini, L.; Taurozzi, M.; Gianotti, N.; Galizzi, N.; Poli, A.; Rusconi, S.; Galli, S. E. S. M.; Rizzardini, G.; Mussini, C.; Menozzi, M.; Gori, A.; Muscatello, A.; Cappelletti, E.; Gargiulo, M.; Garavelli, P. L.; Bargiacchi, O.; Prestileo, T.; Di Lorenzo, F.; Bonanno, S.; Ferrari, C.; degli Antoni, A. M.; Cattelan, A. M.; Gulminetti, R.; Pagnucco, L.; Menichetti, F.; Iapoce, R.; Baldelli, F.; Schiaroli, E.; Italiani, F.; Aquilini, D.; Magnani, G.; Corsini, R.; Barchi, E.; Ferrari, E.; Antinori, A.; Cristaudo, A.; Latini, A.; Cauda, R.; Vullo, V.; Maffongelli, G.; Andreoni, M.; Sassett, L.; Viviani, F.; De Luca, A.; Rossetti, B.; Franco, A.; Resta, F.; Di Perri, G.; Bonora, S.; Bassetti, M.; Londero, A.; Malena, M.; Luzzati, R.
abstract

Objectives: This study evaluated the virological efficacy of dolutegravir 50mg twice daily in 190 HIV-1 failing antiretroviral-experienced patients with previous exposure to first-generation integrase strand transfer inhibitor (INSTI) over a 5 year follow-up using data fromclinical practice. Patients and methods: This analysis included HIV-1-infected patients who were ≥ 18 years of age, treatment experienced, had HIV-1 RNA .50 copies/mL, with INSTI-resistant virus, who started dolutegravir 50mg twice daily plus optimized background therapy (OBT), recorded in the national prospective database PRESTIGIO (www.proget toprestigio.it). Follow-up accrued fromthe start of dolutegravir 50mg twice daily!OBT until virological failure (VF) or dolutegravir discontinuation for any reason or the last treatment visit on dolutegravir 50mg twice daily treatment. VF was defined by the lack of achievement of HIV-1 RNA, 50 copies/mL by 6months and thereafter, or the occurrence of two consecutive HIV-1 RNA ≥50 copies/mL after achievement of undetectable viral load. Results: The estimated VF probabilities were 17% (95% CI=12%-24%), 28% (95% CI=21%-37%), 33% (95% CI=25%-43%), 39% (95% CI=29%-51%) and 52% (95% CI=39%-67%) at 12, 24, 36, 48 and 60months since baseline, respectively. A higher risk of VF was independently associated with baseline viral load .100000 copies/mL (adjusted HR=4.73, 95% CI=1.33-16.78, P=0.016) and with ≥ 1 INSTI mutations plus Q148H/K/R/N and the G140S/A/C as compared with other subjects (adjusted HR=4.18, 95% CI=1.32-13.23, P=0.015). Conclusions: Our data showed a favourable long-term efficacy of dolutegravir 50mg twice daily in association with OBT in treatment-experienced failing subjects, with INSTI-resistant virus, in the real world. A close monitoring of adherence is crucial for maintenance of virological response in this fragile subgroup of subjects.

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 < 0.0001)], CD4+ T cells [R 2 = '0.58, (P < 0.0001)] and CD4/CD8 ratio [R 2 = '0.48, (P < 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 >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 >50 copies/mL) by 24 months (17.2% for >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).

2017 - Virological response and resistance profile in HIV-1-infected patients starting darunavir-containing regimens [Articolo su rivista]
Armenia, D.; Di Carlo, D.; Maffongelli, G.; Borghi, V.; Alteri, C.; Forbici, F.; Bertoli, A.; Gori, C.; Giuliani, M.; Nicastri, E.; Zaccarelli, M.; Pinnetti, C.; Cicalini, S.; D'Offizi, G.; Ceccherini-Silberstein, F.; Mussini, C.; Antinori, A.; Andreoni, M.; Perno, C. F.; Santoro, M. M.
abstract

Objectives: We evaluated the virological response in patients starting a regimen based on darunavir/ritonavir (DRV/r), which is currently the most widely used ritonavir-boosted protease inhibitor. Methods: Data from 206 drug-naïve and 327 PI-experienced patients starting DRV/r 600/100 mg twice daily (DRV600) or 800/100 mg once daily (DRV800) were examined. The probabilities of virological success (VS) and virological rebound (VR) were evaluated in survival analyses. Baseline DRV/r resistance and its evolution at failure were also examined. Results: DRV600 was preferentially administered in patients with complex requirements (older age, higher viraemia, lower CD4 cell count and DRV/PI resistance) compared with DRV800. By 12 months, the probability of achieving VS was 93.2% and 84.3% in drug-naïve and PI-experienced patients, respectively. The higher the baseline viraemia, the longer was the time required to achieve VS, both in drug-naïve patients [>500 000 HIV-1 RNA copies/mL: median [interquartile range (IQR)] 6.1 (5.1–10.3) months; 100 000–500 000 copies/mL: median (IQR) 4.9 (3.8–6.1) months; <100 000 copies/mL: median (IQR) 3.9 (3.5–4.8) months; P < 0.001] and in PI-experienced patients [≥100 000 copies/mL: median (IQR) 7.2 (5.7–11.6) months; <100 000 copies/mL: median (IQR) 2.8 (2.4–3.3) months; P < 0.001]. In PI-experienced patients, the probability of VR was higher for higher viraemia levels (22.3% for ≥100 000 copies/ml vs. 9.7% for <100 000 copies/mL; P = 0.007). Baseline resistance did not affect the virological response. At failure, a high percentage of patients maintained virus susceptible to all PIs (drug-naïve: 95%; PI-experienced: 80%). Despite being used more often in patients with more complex requirements, DRV600 performed as well as DRV800. Conclusions: In clinical practice, use of DRV/r (with its flexible dosage) results in high rates of virological response. These data support the use of PI/r in patients whose characteristics require potent drugs with a high genetic barrier.

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 - Long-term effectiveness of unboosted atazanavir plus abacavir/lamivudine in subjects with virological suppression: A prospective cohort study [Articolo su rivista]
Llibre, J. M.; Cozzi-Lepri, A.; Pedersen, C.; Ristola, M.; Losso, M.; Mocroft, A.; Mitsura, V.; Falconer, K.; Maltez, F.; Beniowski, M.; Vullo, V.; Hassoun, G.; Kuzovatova, E.; Szlavik, J.; Kuznetsova, A.; Stellbrink, H. -J.; Duvivier, C.; Edwards, S.; Laut, K.; Paredes, R.; Losso, M.; Kundro, M.; Vetter, N.; Zangerle, R.; Karpov, I.; Vassilenko, A.; Mitsura, V. M.; Paduto, D.; Clumeck, N.; De Wit, S.; Delforge, M.; Florence, E.; Vandekerckhove, L.; Hadziosmanovic, V.; Kostov, K.; Begovac, J.; Machala, L.; Jilich, D.; Sedlacek, D.; Kronborg, G.; Benfield, T.; Gerstoft, J.; Katzenstein, T.; Moller, N. F.; Pedersen, C.; Ostergaard, L.; Dragsted, U. B.; Nielsen, L. N.; Zilmer, K.; Smidt, J.; Ristola, M.; Aho, I.; Viard, J. -P.; Girard, P. -M.; Cotte, L.; Pradier, C.; Fontas, E.; Dabis, F.; Neau, D.; Duvivier, C.; Rockstroh, J.; Schmidt, R.; Degen, O.; Stellbrink, H. J.; Stefan, C.; Bogner, J.; Fatkenheuer, G.; Chkhartishvili, N.; Kosmidis, J.; Gargalianos, P.; Xylomenos, G.; Lourida, P.; 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.; D'Arminio Monforte, A.; 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.; Ormaasen, V.; Maeland, A.; Bruun, J.; Knysz, B.; Gasiorowski, J.; Inglot, M.; Horban, A.; Bakowska, E.; Flisiak, R.; Grzeszczuk, A.; Parczewski, M.; Pynka, M.; Maciejewska, K.; Beniowski, M.; Mularska, E.; Smiatacz, T.; Gensing, M.; Jablonowska, E.; Malolepsza, E.; Wojcik, K.; Mozer-Lisewska, I.; Doroana, M.; Caldeira, L.; Mansinho, K.; Maltez, F.; Radoi, R.; Oprea, C.; Rakhmanova, A.; Rakhmanova, A.; Trofimora, T.; Khromova, I.; Kuzovatova, E.; Jevtovic, D.; Shunnar, A.; Stanekova, D.; Tomazic, J.; Gatell, J. M.; Miro, J. M.; Moreno, S.; Rodriguez, J. M.; Clotet, B.; 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.; Ledergerber, B.; Weber, R.; Cavassini, M.; Calmy, A.; Furrer, H.; Battegay, M.; Schmid, P.; Kravchenko, E.; Frolov, V.; Kutsyna, G.; Baskakov, I.; Kuznetsova, A.; Kyselyova, G.; Sluzhynska, M.; Gazzard, B.; Johnson, A. M.; Simons, E.; Edwards, S.; Phillips, A.; Johnson, M. A.; Mocroft, A.; Orkin, C.; Weber, J.; Scullard, G.; Clarke, A.; Leen, C.; Lundgren, J.; Grarup, J.; Thiebaut, R.; Burger, D.; Peters, L.; Matthews, C.; Fischer, A. H.; Bojesen, A.; Raben, D.; Kristensen, D.; Larsen, J. F.; Podlekareva, D.; Shepherd, L.; Schultze, A.
abstract

Effectiveness data of an unboosted atazanavir (ATV) with abacavir/lamivudine (ABC/3TC) switch strategy in clinical routine are scant. We evaluated treatment outcomes of ATV + ABC/3TC in pretreated subjects in the EuroSIDA cohort when started with undetectable plasma HIV-1 viral load (pVL), performing a time to loss of virological response (TLOVR <50copies/mL) and a snapshot analysis at 48, 96, and 144 weeks. Virological failure (VF) was defined as confirmed pVL >50copies/mL. We included 285 subjects, 67% male, with median baseline CD4 530 cells, and 44 months with pVL ≤50copies/mL. The third drug in the previous regimen was ritonavir-boosted atazanavir (ATV/r) in 79 (28%), and another ritonavir-boosted protease inhibitor (PI/r) in 29 (10%). Ninety (32%) had previously failed with a PI. Proportions of people with virological success at 48/96/144 weeks were 90%/87%/88% (TLOVR) and 74%/67%/59% (snapshot analysis), respectively. The rates of VF were 8%/8%/6%. Rates of adverse events leading to study discontinuation were 0.4%/1%/2%. The multivariable adjusted analysis showed an association between VF and nadir CD4+ (hazard ratio [HR] 0.63 [95% confidence interval [CI]: 0.42-0.93] per 100 cells higher), time with pVL ≤50copies/mL (HR 0.87 [95% CI: 0.79-0.96] per 6 months longer), and previous failure with a PI (HR 2.78 [95% CI: 1.28-6.04]). Resistance selection at failure was uncommon. A switch to ATV + ABC/3TC in selected subjects with suppressed viremia was associated with low rates of VF and discontinuation due to adverse events, even in subjects not receiving ATV/r. The strategy might be considered in those with long-term suppression and no prior PI failure.

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 >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 - Genotypic tropism testing in HIV-1 proviral DNA can provide useful information at low-level viremia [Articolo su rivista]
Fabeni, L.; Berno, G.; Svicher, V.; Ceccherini-Silberstein, F.; Gori, C.; Bertoli, A.; Mussini, C.; Lichtner, M.; Zaccarelli, M.; Ammassari, A.; Pinnetti, C.; Cicalini, S.; Mastroianni, C. M.; Andreoni, M.; Antinori, A.; Perno, C. F.; Santoro, M. M.
abstract

The possibility of performing genotypic tropism testing (GTT) with proviral DNA (pvDNA) even during suppressed viremia would facilitate the use of CCR5 inhibitors as part of switching, simplification, or intensification strategies. Thus, we aimed to evaluate the tropism concordance between plasma RNA and pvDNA samples and to assess which factors could affect possible discrepancies between the two compartments. GTT was performed using both plasma RNA and pvDNA from 55 sample pairs from drug-experienced patients. Potential differences between the two compartments were evaluated by analyzing coreceptor usage and genetic variability. Paired samples were also stratified in three levels of viremia (<50, 51 to 500, and>500 copies/ml). Overall, Geno2Pheno comparisons of false-positive rates in the two compartments showed good correlation (r=0.72). A high level of concordance in tropism predictions for the two compartments was found (46/55 sample pairs [83.6%]). Among the 9 sample pairs with discordant tropisms, a larger proportion of pvDNA samples harboring CXCR4/dual-mixed-tropic viruses was found, in comparison with plasma RNA samples (88.9% versus 11.1%; P=0.0034). Discordant samples were characterized by greater genetic variability than were concordant samples. With stratification of the paired samples according to viremia levels, the prevalence of discordant samples decreased with increasing viremia (<50 copies/ml, 21.4%; 51 to 500 copies/ml, 15.4%; >500 copies/ml, 6.7%; P=0.2). Our findings confirm that prediction of viral tropism using pvDNA is feasible even in low-level viremia and provides useful information for therapy optimization for patients with low or suppressed viremia.

2015 - Liver-related death among HIV/hepatitis C virus-co-infected individuals: Implications for the era of directly acting antivirals [Articolo su rivista]
Grint, D.; Peters, L.; Rockstroh, J. K.; Rakmanova, A.; Trofimova, T.; Lacombe, K.; Karpov, I.; Galli, M.; Domingo, P.; Kirk, O.; Lundgren, J. D.; Mocrofta, A.; Losso, M.; Kundro, M.; Vetter, N.; Zangerle, R.; Karpov, I.; Vassilenko, A.; Mitsura, V. M.; Paduto, D.; Clumeck, N.; De Wit, S.; Delforge, M.; Florence, E.; Vandekerckhove, L.; Hadziosmanovic, V.; Kostov, K.; Begovac, J.; Machala, L.; Jilich, D.; Sedlacek, D.; Nielsen, J.; Kronborg, G.; Benfield, T.; Larsen, M.; Gerstoft, J.; Katzenstein, T.; Hansen, A. -B. E.; Skinhoj, P.; Pedersen, C.; Moller, N. F.; Ostergaard, L.; Dragsted, U. B.; Nielsen, L. N.; Zilmer, K.; Smidt, J.; Ristola, M.; Katlama, C.; Viard, J. -P.; Girard, P. -M.; Vanhems, P.; Pradier, C.; Dabis, F.; Neau, D.; Duvivier, C.; Rockstroh, J.; Schmidt, R.; Van Lunzen, J.; Degen, O.; Stellbrink, H. J.; Stefan, C.; Bogner, J.; Fatkenheuer, G.; Chkhartishvili, N.; Kosmidis, J.; Gargalianos, P.; Xylomenos, G.; Perdios, J.; Sambatakou, H.; Banhegyi, D.; Gottfredsson, M.; Mulcahy, F.; Yust, I.; Turner, D.; Burke, M.; Shahar, E.; Hassoun, G.; Elinav, H.; Haouzi, M.; Sthoeger, Z. M.; Monforte, A. D.; Esposito, R.; Mazeu, I.; Mussini, C.; Pristera, R.; Mazzotta, F.; Gabbuti, A.; Vullo, V.; Lichtner, M.; Zaccarelli, M.; Antinori, A.; Acinapura, R.; D'Offizi, G.; Lazzarin, A.; Castagna, A.; Gianotti, N.; Galli, M.; Ridolfo, A.; Rozentale, B.; Uzdaviniene, V.; Staub, T.; Hemmer, R.; Reiss, P.; Ormaasen, V.; Maeland, A.; Bruun, J.; Knysz, B.; Gasiorowski, J.; Inglot, M.; Horban, A.; Bakowska, E.; Grzeszczuk, A.; Flisiak, R.; Parczewski, M.; Pynka, M.; Maciejewska, K.; Beniowski, M.; Mularska, E.; Smiatacz, T.; Jablonowska, E.; Malolepsza, E.; Wojcik, K.; Mozer-Lisewska, I.; Doroana, M.; Caldeira, L.; Mansinho, K.; Maltez, F.; Radoi, R.; Oprea, C.; Babes, V.; Rakhmanova, A.; Rakhmanova, A.; Trofimora, T.; Khromova, I.; Kuzovatova, E.; Jevtovic, D.; Shunnar, A.; Stanekova, D.; Tomazic, J.; Moreno, S.; Rodriguez, J. M.; Clotet, B.; Jou, A.; Paredes, R.; Tural, C.; Puig, J.; Bravo, I.; Gatell, J. M.; Miro, J. M.; Domingo, P.; Gutierrez, M.; Mateo, G.; Sambeat, M. A.; Laporte, J. M.; Blaxhult, A.; Flamholc, L.; Thalme, A.; Sonnerborg, A.; Ledergerber, B.; Weber, R.; Cavassini, M.; Calmy, A.; Furrer, H.; Battegay, M.; Elzi, L.; Schmid, P.; Kravchenko, E.; Chentsova, N.; Frolov, V.; Kutsyna, G.; Baskakov, I.; Servitskiy, S.; Kuznetsova, A.; Kyselyova, G.; Gazzard, B.; Johnson, A. M.; Simons, E.; Edwards, S.; Phillips, A.; Johnson, M. A.; Mocroft, A.; Orkin, C.; Weber, J.; Scullard, G.; Fisher, M.; Leen, C.
abstract

Background: Potent, less toxic, directly acting antivirals (DAAs) for treatment of hepatitis C virus (HCV) infection promise to improve HCV cure rates among HIV/ HCV-co-infected individuals. However, the costs of treatment will necessitate prioritization of those at greatest risk of liver-related death (LRD) for therapy. This study aims to provide guidance on who should be prioritized for DAA treatment. Methods: Three thousand, nine hundred and forty-one HCV antibody-positive PSHREG and FIB-4 are names not acronyms (EuroSIDA) patients with follow-up after 1 January 2000 were included, with causes of death classified using Coding causes of Death in HIV (CoDe) methodology. Crude death rates, competing-risks Cox proportional- hazards models and cumulative incidence functions were used to describe factors associated with LRD. Results: LRD accounted for 145 of 670 (21.6%) deaths in the study population. LRD rates peaked in those aged 35'45 years, and occurred almost exclusively in those with at least F2 fibrosis at baseline. In adjustedCoxmodels, risk factors for LRDincluded F4 or F2/F3 fibrosis [sub-distribution hazard ratio (sHR) 6.3, 95%confidence interval (CI)4.1'9.6; andsHR2.5, 95%CI 1.5'4.2 vs. F0/F1, respectively), CD4 cell count (sHR 0.83, 95%CI 0.73'0.95 per doubling) and hepatitis B surface antigen-positive (sHR 2.2, 95% CI 1.3'3.5 vs. hepatitis B surface antigen-negative). The 5-year probability of LRD was low in those with F0/F1 fibrosis (sHR2.2%, 95%CI 1.7''2.9), but substantial in those withF2/F3 and F4 fibrosis (sHR 10.3%, 95% CI 7.6'13.5; and sHR 14.0%, 95% CI 10.3'18.3, respectively). Conclusion: Treatment with DAAs should be prioritized for those with at least F2 fibrosis. Early initiation of cART with the aim of avoiding low CD4 cell counts should be considered essential to decrease the risk of LRD and the need for HCV treatment.

2007 - Determinants of virologic and immunologic outcomes in chronically HIV-infected subjects undergoing repeated treatment interruptions: The Istituto Superiore di Sanità-Pulsed Antiretroviral Therapy (ISS-PART) study [Articolo su rivista]
Palmisano, L.; Giuliano, M.; Bucciardini, R.; Fragola, V.; Andreotti, M.; Galluzzo, C. M.; Pirillo, M. F.; Weimer, L. E.; Arcieri, R.; Germinario, E. A. P.; Amici, R.; Mancini, M. G.; D'Arminio Monforte, A.; Castelli, F.; Caramello, P.; Vella, S.; Abrescia, N.; Figoni, M.; Viglietti, R.; Angarano, G.; Saracino, A.; Anselmo, M.; Antinori, A.; Sette, P.; Zaccarelli, M.; Liuzzi, G.; Arlotti, M.; Martelli, L. T.; Ortolani, P.; Bassetti, D.; Di Biagio, A.; Bisio, F.; Bellissima, P.; Branz, F.; Dorigoni, N.; Cadeo, G.; Vangi, D.; Bertelli, D.; Bergamasco, A.; Caggese, L.; Volonterio, A.; Orofino, G. C.; Carosella, S.; Gennero, L.; Caremani, M.; Tacconi, D.; Carosi, G.; Tomasoni, L.; Patroni, A.; Chiodo, F.; Borderi, M.; Calza, L.; Gritti, F.; Fasulo, G.; Chirianni, A.; Gargiulo, M.; Colomba, A.; Dalle Nogare, E. R.; Di Lorenzo, F.; Prestileo, T.; Bini, T.; Cicconi, P.; De Lalla, F.; Giordani, M. T.; De Stefano, C.; De Stefano, G.; Delia, S.; Ciardi, M.; Di Perri, G.; Sinicco, A.; Sales, P.; Dini, M.; Simeone, M.; Esposito, R.; Guaraldi, G.; Beghetto, B.; Fatuzzo, F.; La Rosa, R.; Ferrari, C.; Calzetti, C.; Ferraro, T.; Cosco, L.; Ghinelli, F.; Sighinolfi, L.; Guadagnino, V.; Caroleo, B.; Izzi, A.; Izzo, C.; Franco, A.; Lazzarin, A.; Castagna, A.; Fusetti, G.; Leoncini, F.; Pozzi, M.; Sbaragli, S.; Marzetti, M.; Magnani, G.; Bonazzi, L.; Barchi, E.; Zoboli, G.; Pintus, A.; Mandas, A.; Soddu, M. L.; Zucca, F.; Mannucci, P. M.; Gringeri, A.; Marani Toro, G.; Graziani, R. V.; Consorti, A.; Mazzotta, F.; Di Pietro, M.; Ble, C.; Meneghetti, F.; Sasset, L.; Cattelan, A. M.; Menichetti, F.; Savalli, E.; Mian, P.; Pristera, R.; Mignani, E.; Artioli, S.; Mura, M. S.; Mannazzu, M.; Narciso, P.; Bellagamba, R.; Orani, A.; Perini, P.; Ortona, L.; De Luca, A.; Murri, R.; Pagano, G.; Alessandrini, A.; Paladini, A.; Vinattieri, M. A.; Carbonai, S.; Pastore, G.; Ladina, N.; Tateo, M.; Piersantelli, N.; Penco, G.; Petrelli, E.; Balducci, M.; Pippi, L.; Gonnelli, A.; Puppo, F.; Murdaca, G.; Raise, E.; Pasquirucci, A.; Riccio, G.; Bartolacci, V.; Carrega, G.; Rizzardini, G.; Migliorino, G.; Russo, R.; Casentino, S.; Celesia, M.; Soranzo, M. L.; Macor, A.; Salassa, B.; Soscia, F.; Roberti, L.; Di Toro, M. T.; Stagno, A.; Beltrami, C.; Suter, F.; Maggiolo, F.; Ripamonti, D.; Tantimonaco, G.; Grisorio, B.; Tassara, A.; Rossi, P.; Tinelli, M.; Regazzetti, A.; Tirelli, U.; Voltaggio, G.; Cinelli, R.; Toti, M.; Baldari, M.; Carli, T.; Ricciardi, B.; Trezzi, M.; Vigevani, G. M.; Capetti, A.; Landonio, S.; Vullo, V.; Massetti, P.; Zauli, T.; Casolari, S.
abstract

BACKGROUND: Factors influencing the outcome of structured treatment interruptions (STIs) in HIV chronic infection are not fully elucidated. METHODS: In ISS-PART, 273 subjects were randomly assigned to arm A (137 assigned to continuous highly active antiretroviral therapy [HAART]) and arm B (136 assigned to 5 STIs of 1, 1, 2, 2, and 3 months' duration, each followed by 3 months of therapy). Main outcome measures were the proportion of subjects with a CD4 count >500 cells/mm, the rate of virologic failure, and the emergence of resistance at 24 months. RESULTS: The proportion of subjects with a CD4 count >500 cells/mm was higher in arm A than in arm B (86.5% vs. 69.1%; P = 0.0075). Pre-HAART CD4 cell count and male gender were independent predictors of a CD4 count >500 cells/mm in arm B. The overall risk of virologic failure was not increased in arm B; however, it was higher in the 38 subjects who had resistance mutations in the rebounding virus. Archived mutations at baseline and the use of a regimen that included an unboosted protease inhibitor (PI), compared with nonnucleoside reverse transcriptase inhibitor-based HAART, independently predicted the emergence of plasma mutations during STI (P = 0.002 for DNA mutations and P = 0.048 for PI-based HAART). CONCLUSIONS: Our results suggest that patients with preexisting mutations and treated with unboosted PI-based HAART should not be enrolled in studies of time-fixed treatment interruptions, being at higher risk of developing plasma mutations during STI and virologic failure at therapy reinstitution. © 2007 Lippincott Williams & Wilkins, Inc.