PLoS Medicine (Jan 2012)

Efficacy and safety of three antiretroviral regimens for initial treatment of HIV-1: a randomized clinical trial in diverse multinational settings.

  • Thomas B Campbell,
  • Laura M Smeaton,
  • N Kumarasamy,
  • Timothy Flanigan,
  • Karin L Klingman,
  • Cynthia Firnhaber,
  • Beatriz Grinsztejn,
  • Mina C Hosseinipour,
  • Johnstone Kumwenda,
  • Umesh Lalloo,
  • Cynthia Riviere,
  • Jorge Sanchez,
  • Marineide Melo,
  • Khuanchai Supparatpinyo,
  • Srikanth Tripathy,
  • Ana I Martinez,
  • Apsara Nair,
  • Ann Walawander,
  • Laura Moran,
  • Yun Chen,
  • Wendy Snowden,
  • James F Rooney,
  • Jonathan Uy,
  • Robert T Schooley,
  • Victor De Gruttola,
  • James Gita Hakim,
  • PEARLS study team of the ACTG

DOI
https://doi.org/10.1371/journal.pmed.1001290
Journal volume & issue
Vol. 9, no. 8
p. e1001290

Abstract

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BackgroundAntiretroviral 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.Methods and findings1,571 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; pConclusionEFV+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.Trial registrationwww.ClinicalTrials.gov NCT00084136. Please see later in the article for the Editors' Summary.