Drug Design, Development and Therapy (May 2016)
Effectiveness, durability, and safety of darunavir/ritonavir in HIV-1-infected patients in routine clinical practice in Italy: a postauthorization noninterventional study
Abstract
Andrea Antinori,1 Paola Meraviglia,2 Antonella d’Arminio Monforte,3,4 Antonella Castagna,5,6 Cristina Mussini,7 Teresa Bini,4 Nicola Gianotti,5 Stefano Rusconi,8 Elisa Colella,8 Giuseppe Airoldi,9 Daniela Mancusi,10 Roberta Termini10 1Clinical Department, National Institute for Infectious Diseases “L. Spallanzani”, Rome, 2Department of Infectious Disease, “L. Sacco” University Hospital, 3Department of Health Sciences – University of Milan, 4Clinic of Infectious Diseases, “San Paolo” Hospital, 5Infectious Diseases, San Raffaele Scientific Institute, 6Università Vita-Salute San Raffaele, Milan, 7Institute of Infectious Diseases, University of Modena and Reggio Emilia, Modena, 8Infectious Diseases Unit, DIBIC Luigi Sacco, University of Milan, 9Studio Associato Airoldi, Cicogna, Ghirri, 10Janssen-Cilag SpA, Medical Affairs, Cologno Monzese, Milan, Italy Abstract: Current antiretroviral (ARV) therapy for the treatment of human immunodeficiency virus (HIV-1)-infected patients provides long-term control of viral load (VL). Darunavir (DRV) is a nonpeptidomimetic protease inhibitor approved for use with a ritonavir booster (DRV/r). This study evaluated the effectiveness of DRV/r in combination with other ARV agents in routine clinical practice in Italy. In this descriptive observational study, data on utilization of DRV/r, under the conditions described in the marketing authorization, were collected from June 2009 to December 2012. Effectiveness (VL <50 copies/mL), tolerability, and durability in four patient groups (two DRV/r-experienced, one ARV-experienced DRV/r-naïve, and one ARV-naïve) were analyzed. Secondary objectives included immunological response, safety, and persistence/discontinuation rates. In total, 875 of 883 enrolled patients were included in the analysis: of these, 662 (75.7%) completed the follow-up until the end of 2012 and 213 (24.3%) withdrew from the study earlier. Initial DRV dose was 600 mg twice daily (67.1%) or 800 mg once daily (32.9%). Only 16 patients (1.8%) withdrew from the study due to virological failure. Virological response proportions were higher in patients virologically suppressed at study entry versus patients with baseline VL ≥50 copies/mL in each ARV-experienced group, while there was no consistent difference across study groups and baseline VL strata according to baseline CD4+ cell count. CD4+ cell count increased from study entry to last study visit in all the four groups. DRV/r was well tolerated, with few discontinuations due to study-emergent nonfatal adverse events (3.0% overall, including 2.1% drug-related) or deaths (3.0% overall, all non-drug-related); 35.3% of patients reported ≥1 adverse events. These observational data show that DRV/r was effective and well tolerated in the whole patient population described here. The DRV/r-containing regimen provided viral suppression in a high percentage of patients in all groups, with low rates of discontinuation due to virological failure. Keywords: darunavir/ritonavir, observational, efficacy, durable, safe
