title: Cobicistat versus ritonavir as a pharmacoenhancer of atazanavir plus emtricitabine/tenofovir disoproxil fumarate in treatment-naive HIV type 1-infected patients: week 48 results.
abstract: BACKGROUND
  Cobicistat (COBI) is a pharmacoenhancer with no antiretroviral activity in vitro.
  
  
  METHODS
  An international, randomized, double-blind, double-dummy, active-controlled trial was conducted to evaluate the efficacy and safety of COBI versus ritonavir (RTV) as a pharmacoenhancer of atazanavir (ATV) in combination with emtricitabine (FTC)/tenofovir disoproxil fumarate (TDF) in treatment-naive patients. The primary end point was a human immunodeficiency virus type 1 (HIV-1) RNA load of <50 copies/mL at week 48 by the Food and Drug Administration snapshot algorithm; the noninferiority margin was 12%.
  
  
  RESULTS
  A total of 692 patients were randomly assigned to a treatment arm and received study drug (344 in the COBI group vs 348 in the RTV group). At week 48, virologic success was achieved in 85% of COBI recipients and 87% of RTV recipients (difference, -2.2% [95% confidence interval, -7.4% to 3.0%]); among patients with a baseline HIV-1 RNA load of >100 000 copies/mL, rates were similar (86% vs 86%). Similar percentages of patients in both groups had serious adverse events (10% of COBI recipients vs 7% of RTV recipients) and adverse events leading to discontinuation of treatment with the study drug (7% vs 7%). Median increases in the serum creatinine level were 0.13 and 0.09 mg/dL, respectively, for COBI and RTV recipients.
  
  
  CONCLUSIONS
  COBI was noninferior to RTV in combination with ATV plus FTC/TDF at week 48. Both regimens achieved high rates of virologic success. Safety and tolerability profiles of the 2 regimens were comparable. Once-daily COBI is a safe and effective pharmacoenhancer of the protease inhibitor ATV.
authors.affiliation: Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. jgallant@jhmi.edu
authors.forename: Joel E
authors.initials: JE
authors.lastname: Gallant
authors.forename: Ellen
authors.initials: E
authors.lastname: Koenig
authors.forename: Jaime
authors.initials: J
authors.lastname: Andrade-Villanueva
authors.forename: Ploenchan
authors.initials: P
authors.lastname: Chetchotisakd
authors.forename: Edwin
authors.initials: E
authors.lastname: DeJesus
authors.forename: Francisco
authors.initials: F
authors.lastname: Antunes
authors.forename: Keikawus
authors.initials: K
authors.lastname: Arastéh
authors.forename: Graeme
authors.initials: G
authors.lastname: Moyle
authors.forename: Giuliano
authors.initials: G
authors.lastname: Rizzardini
authors.forename: Jan
authors.initials: J
authors.lastname: Fehr
authors.forename: Yapei
authors.initials: Y
authors.lastname: Liu
authors.forename: Lijie
authors.initials: L
authors.lastname: Zhong
authors.forename: Christian
authors.initials: C
authors.lastname: Callebaut
authors.forename: Javier
authors.initials: J
authors.lastname: Szwarcberg
authors.forename: Martin S
authors.initials: MS
authors.lastname: Rhee
authors.forename: Andrew K
authors.initials: AK
authors.lastname: Cheng
mesh_terms: D000225:Adenine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D000069446:Atazanavir Sulfate; D002219:Carbamates / Q000008:administration & dosage / Q000627:therapeutic use*; D000069547:Cobicistat; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D000068679:Emtricitabine; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D017320:HIV Protease Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D015497:HIV-1 / Q000187:drug effects; D006801:Humans; D008297:Male; D009842:Oligopeptides / Q000008:administration & dosage / Q000627:therapeutic use*; D063065:Organophosphonates / Q000008:administration & dosage / Q000627:therapeutic use*; D011725:Pyridines / Q000008:administration & dosage / Q000627:therapeutic use*; D019438:Ritonavir / Q000008:administration & dosage / Q000627:therapeutic use*; D000068698:Tenofovir; D013844:Thiazoles / Q000008:administration & dosage / Q000627:therapeutic use*; D016896:Treatment Outcome; D019562:Viral Load / Q000187:drug effects
chemical_list: D019380:Anti-HIV Agents; D002219:Carbamates; D017320:HIV Protease Inhibitors; D009842:Oligopeptides; D063065:Organophosphonates; D011725:Pyridines; D013844:Thiazoles; D003841:Deoxycytidine; D000069446:Atazanavir Sulfate; D000068698:Tenofovir; D000068679:Emtricitabine; D000225:Adenine; D000069547:Cobicistat; D019438:Ritonavir
keywords: HIV; cobicistat; pharmacoenhancer