title: Efficacy and safety of three antiretroviral regimens for initial treatment of HIV-1: a randomized clinical trial in diverse multinational settings.
abstract: BACKGROUND
  Antiretroviral regimens with simplified dosing and better safety are needed to maximize the efficiency of antiretroviral delivery in resource-limited settings. We investigated the efficacy and safety of antiretroviral regimens with once-daily compared to twice-daily dosing in diverse areas of the world.
  
  
  RESULTS
  1,571 HIV-1-infected persons (47% women) from nine countries in four continents were assigned with equal probability to open-label antiretroviral therapy with efavirenz plus lamivudine-zidovudine (EFV+3TC-ZDV), atazanavir plus didanosine-EC plus emtricitabine (ATV+DDI+FTC), or efavirenz plus emtricitabine-tenofovir-disoproxil fumarate (DF) (EFV+FTC-TDF). ATV+DDI+FTC and EFV+FTC-TDF were hypothesized to be non-inferior to EFV+3TC-ZDV if the upper one-sided 95% confidence bound for the hazard ratio (HR) was ≤1.35 when 30% of participants had treatment failure. An independent monitoring board recommended stopping study follow-up prior to accumulation of 472 treatment failures. Comparing EFV+FTC-TDF to EFV+3TC-ZDV, during a median 184 wk of follow-up there were 95 treatment failures (18%) among 526 participants versus 98 failures among 519 participants (19%; HR 0.95, 95% CI 0.72-1.27; p = 0.74). Safety endpoints occurred in 243 (46%) participants assigned to EFV+FTC-TDF versus 313 (60%) assigned to EFV+3TC-ZDV (HR 0.64, CI 0.54-0.76; p<0.001) and there was a significant interaction between sex and regimen safety (HR 0.50, CI 0.39-0.64 for women; HR 0.79, CI 0.62-1.00 for men; p = 0.01). Comparing ATV+DDI+FTC to EFV+3TC-ZDV, during a median follow-up of 81 wk there were 108 failures (21%) among 526 participants assigned to ATV+DDI+FTC and 76 (15%) among 519 participants assigned to EFV+3TC-ZDV (HR 1.51, CI 1.12-2.04; p = 0.007).
  
  
  CONCLUSIONS
  EFV+FTC-TDF had similar high efficacy compared to EFV+3TC-ZDV in this trial population, recruited in diverse multinational settings. Superior safety, especially in HIV-1-infected women, and once-daily dosing of EFV+FTC-TDF are advantageous for use of this regimen for initial treatment of HIV-1 infection in resource-limited countries. ATV+DDI+FTC had inferior efficacy and is not recommended as an initial antiretroviral regimen.
  
  
  BACKGROUND
  www.ClinicalTrials.gov NCT00084136. Please see later in the article for the Editors' Summary.
authors.affiliation: Division of Infectious Diseases, Department of Medicine, University of Colorado School of Medicine, Aurora, United States of America. thomas.campbell@ucdenver.edu
authors.forename: Thomas B
authors.initials: TB
authors.lastname: Campbell
authors.forename: Laura M
authors.initials: LM
authors.lastname: Smeaton
authors.forename: N
authors.initials: N
authors.lastname: Kumarasamy
authors.forename: Timothy
authors.initials: T
authors.lastname: Flanigan
authors.forename: Karin L
authors.initials: KL
authors.lastname: Klingman
authors.forename: Cynthia
authors.initials: C
authors.lastname: Firnhaber
authors.forename: Beatriz
authors.initials: B
authors.lastname: Grinsztejn
authors.forename: Mina C
authors.initials: MC
authors.lastname: Hosseinipour
authors.forename: Johnstone
authors.initials: J
authors.lastname: Kumwenda
authors.forename: Umesh
authors.initials: U
authors.lastname: Lalloo
authors.forename: Cynthia
authors.initials: C
authors.lastname: Riviere
authors.forename: Jorge
authors.initials: J
authors.lastname: Sanchez
authors.forename: Marineide
authors.initials: M
authors.lastname: Melo
authors.forename: Khuanchai
authors.initials: K
authors.lastname: Supparatpinyo
authors.forename: Srikanth
authors.initials: S
authors.lastname: Tripathy
authors.forename: Ana I
authors.initials: AI
authors.lastname: Martinez
authors.forename: Apsara
authors.initials: A
authors.lastname: Nair
authors.forename: Ann
authors.initials: A
authors.lastname: Walawander
authors.forename: Laura
authors.initials: L
authors.lastname: Moran
authors.forename: Yun
authors.initials: Y
authors.lastname: Chen
authors.forename: Wendy
authors.initials: W
authors.lastname: Snowden
authors.forename: James F
authors.initials: JF
authors.lastname: Rooney
authors.forename: Jonathan
authors.initials: J
authors.lastname: Uy
authors.forename: Robert T
authors.initials: RT
authors.lastname: Schooley
authors.forename: Victor
authors.initials: V
authors.lastname: De Gruttola
authors.forename: James Gita
authors.initials: JG
authors.lastname: Hakim
mesh_terms: D019380:Anti-HIV Agents / Q000009:adverse effects* / Q000494:pharmacology / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects*; D060085:Coinfection; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D015658:HIV Infections / Q000188:drug therapy* / Q000382:microbiology / Q000821:virology*; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D038622:Internationality; D008297:Male; D009169:Mycobacterium tuberculosis / Q000502:physiology; D011247:Pregnancy; D013997:Time Factors; D016896:Treatment Outcome; D028761:Withholding Treatment
chemical_list: D019380:Anti-HIV Agents