title: Phase 2 study of cobicistat versus ritonavir each with once-daily atazanavir and fixed-dose emtricitabine/tenofovir df in the initial treatment of HIV infection.
abstract: OBJECTIVE
  To assess efficacy and safety of cobicistat versus ritonavir as pharmacoenhancers for atazanavir when administered with emtricitabine/tenofovir df as initial treatment for HIV-1 infection.
  
  
  METHODS
  Randomized, partially placebo-controlled, double-blind, multicenter study.
  
  
  METHODS
  Antiretroviral treatment-naive adults, screening HIV-1 RNA of at least 5000 copies/ml and CD4 cell count more than 50 cells/μl.
  
  
  METHODS
  Randomized 2 : 1 (stratified by HIV RNA ≤ or >100,000 copies/ml) to receive placebo-blinded once-daily cobicistat 150 mg or ritonavir 100 mg with open-label atazanavir and fixed-dose emtricitabine/tenofovir df.
  
  
  METHODS
  Efficacy and safety at weeks 24 and 48.
  
  
  RESULTS
  Eighty-four percent of ATV/co participants and 86% of ATV/r participants suppressed HIV-1 RNA (<50 copies/ ml) at week 24, and 82 and 86% at week 48, respectively, and mean CD4 cell count increased 203 and 199 cells/μl at week 24 and 208 and 177 cells/μl at week 48, respectively. Study treatment discontinuation due to adverse events occurred in 4% ATV/co and in 3% ATV/r participants through 48 weeks. Treatment-related adverse events occurred in 36% ATV/co and 48% ATV/r participants; hyperbilirubinemia occurred in 96 and 100%, and ocular icterus or jaundice occurred in 14 and 17%, respectively. Mean estimated glomerular filtration rate (Cockcroft-Gault, ml/min) decrease occurred in both treatment groups and was evident at week 2 (ATV/co -9, ATV/r -4), reached a nadir by week 24 (-15, -14, respectively), and did not progress further through week 48 (-13, -14).
  
  
  CONCLUSIONS
  Using cobicistat and ritonavir as pharmacoenhancers for atazanavir and administered with emtricitabine/tenofovir df achieved comparable rates of virologic suppression and CD4 cell count increase with satisfactory safety profiles.
authors.affiliation: Whitman Walker Clinic, Washington, District of Columbia, USA.
authors.forename: Richard
authors.initials: R
authors.lastname: Elion
authors.forename: Calvin
authors.initials: C
authors.lastname: Cohen
authors.forename: Joseph
authors.initials: J
authors.lastname: Gathe
authors.forename: Peter
authors.initials: P
authors.lastname: Shalit
authors.forename: Trevor
authors.initials: T
authors.lastname: Hawkins
authors.forename: Hui C
authors.initials: HC
authors.lastname: Liu
authors.forename: Anita A
authors.initials: AA
authors.lastname: Mathias
authors.forename: Steven L
authors.initials: SL
authors.lastname: Chuck
authors.forename: Brian P
authors.initials: BP
authors.lastname: Kearney
authors.forename: David R
authors.initials: DR
authors.lastname: Warren
mesh_terms: D000225:Adenine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D023241:Antiretroviral Therapy, Highly Active; D000069446:Atazanavir Sulfate; D018791:CD4 Lymphocyte Count; D002219:Carbamates / Q000008:administration & dosage*; D000069547:Cobicistat; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D000068679:Emtricitabine; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D015497:HIV-1; D006801:Humans; D008297:Male; D009842:Oligopeptides / Q000008:administration & dosage*; D063065:Organophosphonates / Q000008:administration & dosage*; D011725:Pyridines / Q000008:administration & dosage*; D012367:RNA, Viral; D019438:Ritonavir / Q000008:administration & dosage*; D000068698:Tenofovir; D013844:Thiazoles / Q000008:administration & dosage*; D016896:Treatment Outcome
chemical_list: D002219:Carbamates; D009842:Oligopeptides; D063065:Organophosphonates; D011725:Pyridines; D012367:RNA, Viral; D013844:Thiazoles; D003841:Deoxycytidine; D000069446:Atazanavir Sulfate; D000068698:Tenofovir; D000068679:Emtricitabine; D000225:Adenine; D000069547:Cobicistat; D019438:Ritonavir