title: Effectiveness, durability, and safety of darunavir/ritonavir in HIV-1-infected patients in routine clinical practice in Italy: a postauthorization noninterventional study.
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.
authors.affiliation: Clinical Department, National Institute for Infectious Diseases "L. Spallanzani", Rome, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Antinori
authors.affiliation: Department of Infectious Disease, "L. Sacco" University Hospital, Milan, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Meraviglia
authors.affiliation: Department of Health Sciences - University of Milan, Milan, Italy; Clinic of Infectious Diseases, "San Paolo" Hospital, Milan, Italy.
authors.forename: Antonella d'Arminio
authors.initials: Ad
authors.lastname: Monforte
authors.affiliation: Infectious Diseases, San Raffaele Scientific Institute, Milan, Italy; Università Vita-Salute San Raffaele, Milan, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Castagna
authors.affiliation: Institute of Infectious Diseases, University of Modena and Reggio Emilia, Modena, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Mussini
authors.affiliation: Clinic of Infectious Diseases, "San Paolo" Hospital, Milan, Italy.
authors.forename: Teresa
authors.initials: T
authors.lastname: Bini
authors.affiliation: Infectious Diseases, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Nicola
authors.initials: N
authors.lastname: Gianotti
authors.affiliation: Infectious Diseases Unit, DIBIC Luigi Sacco, University of Milan, Cicogna, Ghirri, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Rusconi
authors.affiliation: Infectious Diseases Unit, DIBIC Luigi Sacco, University of Milan, Cicogna, Ghirri, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Colella
authors.affiliation: Studio Associato Airoldi, Cicogna, Ghirri, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Airoldi
authors.affiliation: Janssen-Cilag SpA, Medical Affairs, Cologno Monzese, Milan, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Mancusi
authors.affiliation: Janssen-Cilag SpA, Medical Affairs, Cologno Monzese, Milan, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Termini
mesh_terms: D044966:Anti-Retroviral Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D000069454:Darunavir / Q000009:adverse effects* / Q000494:pharmacology*; D004334:Drug Administration Schedule; D015658:HIV Infections / Q000188:drug therapy*; D017320:HIV Protease Inhibitors / Q000009:adverse effects* / Q000494:pharmacology; D015497:HIV-1 / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D007558:Italy; D064887:Observational Studies as Topic; D012367:RNA, Viral / Q000737:chemistry* / Q000378:metabolism; D019438:Ritonavir / Q000009:adverse effects* / Q000494:pharmacology*
chemical_list: D044966:Anti-Retroviral Agents; D017320:HIV Protease Inhibitors; D012367:RNA, Viral; D019438:Ritonavir; D000069454:Darunavir
keywords: darunavir/ritonavir; durable; efficacy; observational; safe