1. Efficacy and Safety of Three Antiretroviral Regimens for Initial Treatment of HIV-1: A Randomized Clinical Trial in Diverse Multinational Settings
- Author
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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, and Faesen, Sharla
- Subjects
Biomedical and Clinical Sciences ,Clinical Sciences ,Patient Safety ,Infectious Diseases ,Comparative Effectiveness Research ,HIV/AIDS ,Clinical Trials and Supportive Activities ,Clinical Research ,6.1 Pharmaceuticals ,Evaluation of treatments and therapeutic interventions ,Infection ,Anti-HIV Agents ,Antiretroviral Therapy ,Highly Active ,Coinfection ,Drug Therapy ,Combination ,Female ,Follow-Up Studies ,HIV Infections ,HIV-1 ,Humans ,Internationality ,Male ,Mycobacterium tuberculosis ,Pregnancy ,Time Factors ,Treatment Outcome ,Withholding Treatment ,PEARLS study team of the ACTG ,Medical and Health Sciences ,General & Internal Medicine ,Biomedical and clinical sciences ,Health sciences - 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
- Published
- 2012