Please use this identifier to cite or link to this item:
Title: Efficacy and Safety of Three Antiretroviral Regimens for Initial Treatment of HIV-1: A Randomized Clinical Trial in Diverse Multinational Settings
Authors: Thomas B. Campbell
Laura M. Smeaton
N. Kumarasamy
Timothy Flanigan
Karin L. Klingman
Cynthia Firnhaber
Beatriz Grinsztejn
Mina C. Hosseinipour
Johnstone Kumwenda
Umesh Lalloo
Cynthia Riviere
Jorge Sanchez
Marineide Melo
Khuanchai Supparatpinyo
Srikanth Tripathy
Ana I. Martinez
Apsara Nair
Ann Walawander
Laura Moran
Yun Chen
Wendy Snowden
James F. Rooney
Jonathan Uy
Robert T. Schooley
Victor de Gruttola
James Gita Hakim
Edith Swann
Ronald L. Barnett
Barbara Brizz
Yvette Delph
Nikki Gettinger
Ronald T. Mitsuyasu
Susan Eshleman
Steven Safren
Susan A. Fiscus
Adriana Andrade
David W. Haas
Farida Amod
Vladimir Berthaud
Robert C. Bollinger
Yvonne Bryson
David Celentano
David Chilongozi
Myron Cohen
Ann C. Collier
Judith Silverstein Currier
Susan Cu-Uvin
Joseph Eron
Charles Flexner
Joel E. Gallant
Roy M. Gulick
Scott M. Hammer
Irving Hoffman
Peter Kazembe
Newton Kumwenda
Javier R. Lama
Jody Lawrence
Chiedza Maponga
Francis Martinson
Kenneth Mayer
Karin Nielsen
Richard B. Pendame
Bharat Ramratnam
Ian Sanne
Patrice Severe
Thira Sirisanthana
Suniti Solomon
Steve Tabet
Taha Taha
Charles van der Horst
Christine Wanke
Joan Gormley
Cheryl J. Marcus
Beverly Putnam
Smanga Ntshele
Edde Loeliger
Keith A. Pappa
Nancy Webb
David L. Shugarts
Mark A. Winters
Renard S. Descallar
Joseph Steele
Michael Wulfsohn
Farideh Said
Yue Chen
John C. Martin
Norbert Bischofberger
Andrew Cheng
Howard Jaffe
Jabin Sharma
S. Poongulali
Sandra Wagner Cardoso
Deise Lucia Faria
Sima Berendes
Kelly Burke
Rosie Mngqibisa
Cecelia Kanyama
Virginia Kayoyo
Wadzanai P. Samaneka
Anthony Chisada
Keywords: Medicine
Issue Date: 1-Aug-2012
Abstract: 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: NCT00084136. © 2012.
ISSN: 15491676
Appears in Collections:CMUL: Journal Articles

Files in This Item:
There are no files associated with this item.

Items in CMUIR are protected by copyright, with all rights reserved, unless otherwise indicated.