1. Efficacy and Safety of Three Antiretroviral Regimens for Initial Treatment of HIV-1: A Randomized Clinical Trial in Diverse Multinational Settings
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David Chilongozi, Sharla Faesen, Breno Santos, Mamta K. Jain, Pablo Tebas, Apsara Nair, Cynthia Riviere, Beatriz Grinsztejn, Sima Berendes, Steve Tabet, Joan Gormley, M. Graham Ray, Johnstone Kumwenda, Judith Feinberg, Todd Stroberg, Kenneth H. Mayer, Nikki Gettinger, Vicki L. Bailey, James Hakim, Selvamuthu Poongulali, Sandra W. Cardoso, Marineide Gonçalves de Melo, Karin L. Klingman, Rosie Mngqibisa, Thomas B. Campbell, Amneris E. Luque, Beverly Putnam, Thira Sirisanthana, Janice M. Fritsche, Ann Walawander, Ge Youl Kim, Roberto Corales, Richard B. Pollard, Ronald T. Mitsuyasu, Martha Silberman, Rita Alves Lira, Janet Forcht, Norbert Bischofberger, Ana Martinez, Barbara Brizz, Laura M. Smeaton, Asmita Gaikwad, Farida Amod, Srikanth Tripathy, Babafemi Taiwo, Anthony Chisada, Chiedza Maponga, Charles van der Horst, Michael Wulfsohn, Javier R. Lama, Taha E. Taha, Manuel Revuelta, Christine Hurley, David Currin, Wendy Snowden, Keith A. Pappa, Rosa Infante, T. Petersen, Donna V. McGregor, Susan Cu-Uvin, Susan A. Fiscus, Eric S. Daar, Jody Lawrence, P. Jan Geiseler, Irving F. Hoffman, Luis Lopez-Detres, Karen T. Tashima, Larisa Zifchak, Victor De Gruttola, Timothy P. Flanigan, Laura Moran, Farideh Said, Alberto La Rosa, Raman R. Gangakhedkar, Maria Palmer, Michael F. Para, Joel E. Gallant, Nancy Webb, Cecilia Kanyama, Wadzanai Samaneka, Jabin Sharma, Yvonne J. Bryson, Mark A. Winters, Ian Sanne, David Shugarts, Yun Chen, Sampada Dhayarkar, Peter N. Kazembe, Scott M. Hammer, Adriana Andrade, Robert T. Schooley, Beth D. Mullan, Henry H. Balfour, Patrice Severe, Beverly E. Sha, Madeline Torres, Cathi Basler, Andrew K. Cheng, Jolene Noel-Connor, Vladimir Berthaud, Jonathan Uy, Michael K. Klebert, Virginia Kayoyo, Donna Mildvan, David W. Haas, Joseph J. Eron, Cheryl Mogridge, David D. Celentano, Ruben Lopez, Ronald L. Barnett, Karin Nielsen, Helen Patterson, Renard S. Descallar, Jenifer Baer, Deise Lucia Faria, Cheryl Marcus, Khuanchai Supparatpinyo, Mina C. Hosseinipour, Newton Kumwenda, Yvette Delph, Smanga Ntshele, Edith Swann, Steven A. Safren, David M. Asmuth, Kelly Burke, Laurie Frarey, Joseph Steele, Gary M. Cox, Umesh G. Lalloo, Richard B. Pendame, Mary Adams, Bharat Ramratnam, Christine Wanke, James F. Rooney, Francis Martinson, Edde Loeliger, Anjali A. Joglekar, John Martin, Myron S. Cohen, Sheela Godbole, Robert C. Bollinger, Roy M. Gulick, Cynthia Firnhaber, Charles Flexner, William A. O'Brien, Suniti Solomon, Jorge Sanchez, Yue Chen, Susan H. Eshleman, Kathy J. Watson, N. Kumarasamy, David H. Haas, Ann C. Collier, Bartolo Santos, Suwat Chariyalertsak, Michelle S. Cespedes, Howard Jaffe, Judith S. Currier, and Deeks, Steven G
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Male ,Comparative Effectiveness Research ,Time Factors ,Internationality ,HIV Infections ,Medical and Health Sciences ,law.invention ,chemistry.chemical_compound ,0302 clinical medicine ,Randomized controlled trial ,Pregnancy ,law ,030212 general & internal medicine ,0303 health sciences ,education.field_of_study ,Coinfection ,Hazard ratio ,virus diseases ,General Medicine ,3. Good health ,Infectious Diseases ,Treatment Outcome ,6.1 Pharmaceuticals ,Combination ,HIV/AIDS ,Medicine ,Female ,Patient Safety ,Infection ,medicine.drug ,medicine.medical_specialty ,Efavirenz ,Anti-HIV Agents ,Clinical Trials and Supportive Activities ,Population ,Antiretroviral Therapy ,Emtricitabine ,03 medical and health sciences ,Drug Therapy ,Clinical Research ,General & Internal Medicine ,Internal medicine ,PEARLS study team of the ACTG ,medicine ,Humans ,Highly Active ,Dosing ,education ,030306 microbiology ,business.industry ,Evaluation of treatments and therapeutic interventions ,Mycobacterium tuberculosis ,Surgery ,Atazanavir ,Regimen ,Withholding Treatment ,chemistry ,HIV-1 ,business ,Follow-Up Studies - 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; pConclusionEFV+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 registrationwww.ClinicalTrials.gov NCT00084136. Please see later in the article for the Editors' Summary.
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- 2012