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Efficacy and safety of three antiretroviral regimens for initial treatment of HIV-1: a randomized clinical trial in diverse multinational settings Full Text
PLoS Medicine, 08/17/2012
Campbell TB et al. – 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.
Methods- 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).