title: Randomized, phase 2 evaluation of two single-tablet regimens elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate versus efavirenz/emtricitabine/tenofovir disoproxil fumarate for the initial treatment of HIV infection.
abstract: OBJECTIVE
  To assess the safety and efficacy of two, single-tablet regimens for the initial treatment of HIV infection.
  
  
  METHODS
  Phase 2, randomized, double-blind, double-dummy, multicenter, active-controlled study.
  
  
  METHODS
  Antiretroviral treatment-naive adults with a screening HIV-1 RNA at least 5000 copies/ml and a CD4 cell count more than 50 cells/μl were randomized 2: 1 to receive fixed-dose combination tablets of elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate (EVG/COBI/FTC/TDF; N = 48) or efavirenz/emtricitabine/tenofovir disoproxil fumarate (EFV/FTC/TDF; n = 23) for 48 weeks. The primary endpoint was proportion of participants with HIV-1 RNA less than 50 copies/ml at week 24.
  
  
  RESULTS
  Participants receiving EVG/COBI/FTC/TDF exhibited a more rapid decline in HIV-1 RNA and a greater proportion suppressed viral load to less than 50 copies/ml than participants receiving EFV/FTC/TDF. Both EVG/COBI/FTC/TDF and EFV/FTC/TDF resulted in high rates of viral suppression and increases in CD4 cell count. Ninety and 83% of participants suppressed HIV-1 RNA to less than 50 copies/ml both at the 24-week and 48-week visits for EVG/COBI/FTC/TDF and EFV/FTC/TDF, respectively. Once-daily administration of EVG/COBI/FTC/TDF provided a mean EVG trough concentration 10-fold over its protein binding-adjusted IC(95) across study visits. EVG/FTC/TDF/GS-9350 was generally well tolerated with a lower rate of drug-related central nervous system (17%) and psychiatric (10%) adverse events versus EFV/FTC/TDF (26 and 44%, respectively). Decreases in estimated glomerular filtration rate occurred within the first few weeks of dosing in participants receiving EVG/COBI/FTC/TDF, remained within the normal range and did not progress at week 24 or 48; no participant experienced a clinical adverse event or discontinued study drug due to changes in serum creatinine or renal function.
  
  
  CONCLUSIONS
  Once-daily EVG/COBI/FTC/TDF achieved and maintained a high rate of virologic suppression with fewer central nervous system and psychiatric adverse events compared to a current standard-of-care regimen of EFV/FTC/TDF.
authors.affiliation: Gilead Sciences Inc., Foster City, California, USA.
authors.forename: Calvin
authors.initials: C
authors.lastname: Cohen
authors.forename: Richard
authors.initials: R
authors.lastname: Elion
authors.forename: Peter
authors.initials: P
authors.lastname: Ruane
authors.forename: David
authors.initials: D
authors.lastname: Shamblaw
authors.forename: Edwin
authors.initials: E
authors.lastname: DeJesus
authors.forename: Bruce
authors.initials: B
authors.lastname: Rashbaum
authors.forename: Steven L
authors.initials: SL
authors.lastname: Chuck
authors.forename: Kitty
authors.initials: K
authors.lastname: Yale
authors.forename: Hui C
authors.initials: HC
authors.lastname: Liu
authors.forename: David R
authors.initials: DR
authors.lastname: Warren
authors.forename: Srinivasan
authors.initials: S
authors.lastname: Ramanathan
authors.forename: Brian P
authors.initials: BP
authors.lastname: Kearney
mesh_terms: D000225:Adenine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D000328:Adult; D000480:Alkynes; D019380:Anti-HIV Agents; D048588:Benzoxazines / Q000008:administration & dosage* / Q000494:pharmacology; D018791:CD4 Lymphocyte Count; D002219:Carbamates / Q000008:administration & dosage; D000069547:Cobicistat; D003521:Cyclopropanes; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D004338:Drug Combinations; D000068679:Emtricitabine; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D015497:HIV-1; D006801:Humans; D008297:Male; D063065:Organophosphonates / Q000008:administration & dosage* / Q000494:pharmacology; D010349:Patient Compliance; D018579:Patient Selection; D015363:Quinolones / Q000008:administration & dosage; D000068698:Tenofovir; D013844:Thiazoles / Q000008:administration & dosage; D016896:Treatment Outcome
chemical_list: D000480:Alkynes; D019380:Anti-HIV Agents; D048588:Benzoxazines; D002219:Carbamates; D003521:Cyclopropanes; D004338:Drug Combinations; D063065:Organophosphonates; D015363:Quinolones; D013844:Thiazoles; D003841:Deoxycytidine; C509700:elvitegravir; D000068698:Tenofovir; D000068679:Emtricitabine; D000225:Adenine; C098320:efavirenz; D000069547:Cobicistat