Efficacy and Safety of Three Antiretroviral Regimens for Initial Treatment of HIV-1: A Randomized Clinical Trial in Diverse Multinational Settings

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.methods and findings: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).conclusion: 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.trial registration:http://www.clinicaltrials.gov nct00084136. © 2012.