학술논문
Efficacy and Safety of Three Antiretroviral Regimens for Initial Treatment of HIV-1: A Randomized Clinical Trial in Diverse Multinational Settings
Document Type
article
Author
Campbell, Thomas B; Smeaton, Laura M; Kumarasamy, N; Flanigan, Timothy; Klingman, Karin L; Firnhaber, Cynthia; Grinsztejn, Beatriz; Hosseinipour, Mina C; Kumwenda, Johnstone; Lalloo, Umesh; Riviere, Cynthia; Sanchez, Jorge; Melo, Marineide; Supparatpinyo, Khuanchai; Tripathy, Srikanth; Martinez, Ana I; Nair, Apsara; Walawander, Ann; Moran, Laura; Chen, Yun; Snowden, Wendy; Rooney, James F; Uy, Jonathan; Schooley, Robert T; De Gruttola, Victor; Hakim, James Gita; Swann, Edith; Barnett, Ronald L; Brizz, Barbara; Delph, Yvette; Gettinger, Nikki; Mitsuyasu, Ronald T; Eshleman, Susan; Safren, Steven; Fiscus, Susan A; Andrade, Adriana; Haas, David W; Amod, Farida; Berthaud, Vladimir; Bollinger, Robert C; Bryson, Yvonne; Celentano, David; Chilongozi, David; Cohen, Myron; Collier, Ann C; Currier, Judith Silverstein; Cu-Uvin, Susan; Eron, Joseph; Flexner, Charles; Gallant, Joel E; Gulick, Roy M; Hammer, Scott M; Hoffman, Irving; Kazembe, Peter; Kumwenda, Newton; Lama, Javier R; Lawrence, Jody; Maponga, Chiedza; Martinson, Francis; Mayer, Kenneth; Nielsen, Karin; Pendame, Richard B; Ramratnam, Bharat; Sanne, Ian; Severe, Patrice; Sirisanthana, Thira; Solomon, Suniti; Tabet, Steve; Taha, Taha; van der Horst, Charles; Wanke, Christine; Gormley, Joan; Marcus, Cheryl J; Putnam, Beverly; Loeliger, Edde; Pappa, Keith A; Webb, Nancy; Shugarts, David L; Winters, Mark A; Descallar, Renard S; Steele, Joseph; Wulfsohn, Michael; Said, Farideh; Chen, Yue; Martin, John C; Bischofberger, Norbert; Cheng, Andrew; Jaffe, Howard; Sharma, Jabin; Poongulali, S; Cardoso, Sandra Wagner; Faria, Deise Lucia; Berendes, Sima; Burke, Kelly; Mngqibisa, Rosie; Kanyama, Cecelia; Kayoyo, Virginia; Samaneka, Wadzanai P; Chisada, Anthony; Faesen, Sharla
Source
PLOS Medicine. 9(8)
Subject
Language
Abstract
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; p