Efficacy and Safety of Three Antiretroviral Regimens for Initial Treatment of HIV-1: A Randomized Clinical Trial in Diverse Multinational Settings
Creators: name: Firnhaber, C.
name: Torres, M.
name: Santos, B.
name: Webb, N.
name: Mildvan, D.
name: Nair, A.
name: Hoffman, I.
name: McGregor, D.
name: Chariyalertsak, S.
name: Stroberg, T.
name: Martinez, A.I.
name: Infante, R.
name: Para, M.F.
name: Hurley, C.
name: Marcus, C.J.
name: Poongulali, S.
name: Eshleman, S.
name: Andrade, A.
name: Lira, R.A.
name: Tashima, K.T.
name: Lawrence, J.
name: Cohen, M.
name: Swann, E.
name: Noel-Connor, J.
name: Steele, J.
name: Mitsuyasu, R.T.
name: Lalloo, U.
name: Cu-Uvin, S.
name: Riviere, C.
name: Amod, F.
name: Shugarts, D.L.
name: Descallar, R.S.
name: Klingman, K.L.
name: Gormley, J.
name: Corales, R.
name: Luque, A.
name: Smeaton, L.M.
name: Currier, J.S.
name: Said, F.
name: Haas, D.W.
name: Campbell, T.B.
name: Dhayarkar, S.
name: Celentano, D.
name: Sanne, I.
name: Tabet, S.
name: Jain, M.
name: Daar, E.S.
name: Kumwenda, N.
name: Revuelta, M.
name: Kayoyo, V.
name: Feinberg, J.
name: Taha, T.
name: Chilongozi, D.
name: Kazembe, P.
name: Cardoso, S.W.
name: Martinson, F.
name: Berendes, S.
name: Faesen, S.
name: Schooley, R.T.
name: Flanigan, T.
name: Bischofberger, N.
name: Walawander, A.
name: Kumwenda, J.
name: Supparatpinyo, K.
name: Lama, J.R.
name: Pappa, K.A.
name: Klebert, M.K.
name: Severe, P.
name: Berthaud, V.
name: Solomon, S.
name: Petersen, T.
name: la Rosa, A.
name: Frarey, L.
name: Cheng, A.
name: van der Horst, C.
name: Barnett, R.L.
name: Sharma, J.
name: Putnam, B.
name: Fiscus, S.A.
name: Chen, Y.
name: Gaikwad, A.
name: Brizz, B.
name: Chisada, A.
name: Cox, G.M.
name: Uy, J.
name: Adams, M.
name: Moran, L.
name: Bailey, V.L.
name: Rooney, J.F.
name: Snowden, W.
name: Pollard, R.B.
name: Wulfsohn, M.
name: Mayer, K.
name: Chen, Y.
name: Gettinger, N.
name: Watson, K.J.
name: Sha, B.E.
name: Ray, M.G.
name: Hakim, J.G.
name: Palmer, M.
name: Kim, G.-Y.
name: Basler, C.
name: Lopez-Detres, L.
name: Samaneka, W.P.
name: Bollinger, R.C.
name: Delph, Y.
name: Wanke, C.
name: Bryson, Y.
name: Faria, D.L.
name: Mogridge, C.
name: Taiwo, B.
name: Nielsen, K.
name: Forcht, J.
name: Winters, M.A.
name: de Gruttola, V.
name: Tebas, P.
name: Lopez, R.
name: Ntshele, S.
name: Asmuth, D.
name: Godbole, S.
name: Patterson, H.
name: Flexner, C.
name: Eron, J.
name: Collier, A.C.
name: Ramratnam, B.
name: Tripathy, S.
name: Jaffe, H.
name: Balfour, H.H.
name: Zifchak, L.
name: Kumarasamy, N.
name: Haas, D.H.
name: Fritsche, J.M.
name: Currin, D.
name: Grinsztejn, B.
name: Mngqibisa, R.
name: Gangakhedkar, R.R.
name: Gallant, J.E.
name: Martin, J.C.
name: Safren, S.
name: Silberman, M.
name: Mullan, B.
name: Geiseler, P.J.
name: Joglekar, A.A.
name: Cespedes, M.
name: Kanyama, C.
name: Gulick, R.M.
name: Burke, K.
name: Maponga, C.
name: Loeliger, E.
name: Hosseinipour, M.C.
name: Baer, J.
name: OBrien, W.A.
name: Santos, B.
name: Melo, M.
name: Pendame, R.B.
name: Hammer, S.M.
name: Sanchez, J.
name: Sirisanthana, T.
Publisher: name: Public Library of Science
Year: 2012

description: 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 â‰¤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.