title: Co-formulated elvitegravir, cobicistat, emtricitabine, and tenofovir versus co-formulated efavirenz, emtricitabine, and tenofovir for initial treatment of HIV-1 infection: a randomised, double-blind, phase 3 trial, analysis of results after 48 weeks.
abstract: BACKGROUND
  The integrase inhibitor elvitegravir (EVG) has been co-formulated with the CYP3A4 inhibitor cobicistat (COBI), emtricitabine (FTC), and tenofovir disoproxil fumarate (TDF) in a single tablet given once daily. We compared the efficacy and safety of EVG/COBI/FTC/TDF with standard of care-co-formulated efavirenz (EFV)/FTC/TDF-as initial treatment for HIV infection.
  
  
  METHODS
  In this phase 3 trial, treatment-naive patients from outpatient clinics in North America were randomly assigned by computer-generated allocation sequence with a block size of four in a 1:1 ratio to receive EVG/COBI/FTC/TDF or EFV/FTC/TDF, once daily, plus matching placebo. Patients and study staff involved in giving study treatment, assessing outcomes, and collecting and analysing data were masked to treatment allocation. Eligibility criteria included screening HIV RNA concentration of 5000 copies per mL or more, and susceptibility to efavirenz, emtricitabine, and tenofovir. The primary endpoint was HIV RNA concentration of fewer than 50 copies per mL at week 48. The study is registered with ClinicalTrials.gov, number NCT01095796.
  
  
  RESULTS
  700 patients were randomly assigned and treated (348 with EVG/COBI/FTC/TDF, 352 with EFV/FTC/TDF). EVG/COBI/FTC/TDF was non-inferior to EFV/FTC/TDF; 305/348 (87·6%) versus 296/352 (84·1%) of patients had HIV RNA concentrations of fewer than 50 copies per mL at week 48 (difference 3·6%, 95% CI -1·6% to 8·8%). Proportions of patients discontinuing drugs for adverse events did not differ substantially (13/348 in the EVG/COBI/FTC/TDF group vs 18/352 in the EFV/FTC/TDF group). Nausea was more common with EVG/COBI/FTC/TDF than with EFV/FTC/TDF (72/348 vs 48/352) and dizziness (23/348 vs 86/352), abnormal dreams (53/348 vs 95/352), insomnia (30/348 vs 49/352), and rash (22/348 vs 43/352) were less common. Serum creatinine concentration increased more by week 48 in the EVG/COBI/FTC/TDF group than in the EFV/FTC/TDF group (median 13 μmol/L, IQR 5 to 20 vs 1 μmol/L, -6 to 8; p<0·001).
  
  
  CONCLUSIONS
  If regulatory approval is given, EVG/COBI/FTC/TDF would be the only single-tablet, once-daily, integrase-inhibitor-based regimen for initial treatment of HIV infection.
  
  
  BACKGROUND
  Gilead Sciences.
authors: Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. Electronic address: psax@partners.org.
authors: Paul E
authors: PE
authors: Sax
authors: Orlando Immunology Center, Orlando, FL, USA.
authors: Edwin
authors: E
authors: DeJesus
authors: Anthony Mills MD, Los Angeles, CA, USA.
authors: Anthony
authors: A
authors: Mills
authors: Stanford University, Palo Alto, CA, USA.
authors: Andrew
authors: A
authors: Zolopa
authors: Community Research Initiative of New England, Boston, MA, USA.
authors: Calvin
authors: C
authors: Cohen
authors: University of North Carolina, Chapel Hill, NC, USA.
authors: David
authors: D
authors: Wohl
authors: University of North Carolina, Chapel Hill, NC, USA.
authors: Joel E
authors: JE
authors: Gallant
authors: Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors: Hui C
authors: HC
authors: Liu
authors: Gilead Sciences, Foster City, CA, USA.
authors: Lijie
authors: L
authors: Zhong
authors: Gilead Sciences, Foster City, CA, USA.
authors: Kitty
authors: K
authors: Yale
authors: Gilead Sciences, Foster City, CA, USA.
authors: Kirsten
authors: K
authors: White
authors: Gilead Sciences, Foster City, CA, USA.
authors: Brian P
authors: BP
authors: Kearney
authors: Gilead Sciences, Foster City, CA, USA.
authors: Javier
authors: J
authors: Szwarcberg
authors: Gilead Sciences, Foster City, CA, USA.
authors: Erin
authors: E
authors: Quirk
authors: Gilead Sciences, Foster City, CA, USA.
authors: Andrew K
authors: AK
authors: Cheng
mesh_terms: D000225:Adenine / Q000008:administration & dosage / Q000031:analogs & derivatives; D000328:Adult; D000480:Alkynes; D019380:Anti-HIV Agents / Q000008:administration & dosage*; D048588:Benzoxazines / Q000008:administration & dosage; D002219:Carbamates / Q000008:administration & dosage; D000069547:Cobicistat; D003521:Cyclopropanes; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D004311:Double-Blind Method; D004338:Drug Combinations; D000068679:Emtricitabine; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D015497:HIV-1; D006801:Humans; D008297:Male; D008875:Middle Aged; D063065:Organophosphonates / Q000008:administration & dosage; D015363:Quinolones / Q000008:administration & dosage; D000068698:Tenofovir; D013844:Thiazoles / Q000008:administration & dosage
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