Efficacy and Safety of Three Antiretroviral Regimens for Initial Treatment of HIV-1: A Randomized Clinical Trial in Diverse Multinational Settings

نویسندگان

  • 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
  • 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
  • Sharla Faesen
  • Suwat Chariyalertsak
  • Breno Santos
  • Rita Alves Lira
  • Anjali A. Joglekar
  • Alberto La Rosa
  • Rosa Infante
  • Mamta Jain
  • Tianna Petersen
  • Sheela Godbole
  • Sampada Dhayarkar
  • Judith Feinberg
  • Jenifer Baer
  • Richard B. Pollard
  • David Asmuth
  • Raman R Gangakhedkar
  • Asmita Gaikwad
  • M. Graham Ray
  • Cathi Basler
  • Michael F. Para
  • Kathy J. Watson
  • Babafemi Taiwo
  • Donna McGregor
  • Henry H. Balfour
  • Beth Mullan
  • Ge-Youl Kim
  • Michael K. Klebert
  • Gary Matthew Cox
  • Martha Silberman
  • Donna Mildvan
  • Manuel Revuelta
  • Karen T. Tashima
  • Helen Patterson
  • P. Jan Geiseler
  • Bartolo Santos
  • Eric S Daar
  • Ruben Lopez
  • Laurie Frarey
  • David Currin
  • David H. Haas
  • Vicki L. Bailey
  • Pablo Tebas
  • Larisa Zifchak
  • Jolene Noel-Connor
  • Madeline Torres
  • Beverly E. Sha
  • Janice M. Fritsche
  • Michelle Cespedes
  • Janet Forcht
  • William A. O'Brien
  • Cheryl Mogridge
  • Christine Hurley
  • Roberto Corales
  • Maria Palmer
  • Mary Adams
  • Amneris Luque
  • Luis Lopez-Detres
  • Todd Stroberg
چکیده

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 www.ClinicalTrials.gov NCT00084136. Please see later in the article for the Editors' Summary.

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عنوان ژورنال:

دوره 9  شماره 

صفحات  -

تاریخ انتشار 2012