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

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 area...

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Main 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
Format: Journal
Published: 2018
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http://cmuir.cmu.ac.th/jspui/handle/6653943832/51864
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Institution: Chiang Mai University
id th-cmuir.6653943832-51864
record_format dspace
institution Chiang Mai University
building Chiang Mai University Library
country Thailand
collection CMU Intellectual Repository
topic Medicine
spellingShingle Medicine
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
Efficacy and Safety of Three Antiretroviral Regimens for Initial Treatment of HIV-1: A Randomized Clinical Trial in Diverse Multinational Settings
description 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:http://www.ClinicalTrials.gov NCT00084136. © 2012.
format Journal
author 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
author_facet 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
author_sort Thomas B. Campbell
title Efficacy and Safety of Three Antiretroviral Regimens for Initial Treatment of HIV-1: A Randomized Clinical Trial in Diverse Multinational Settings
title_short Efficacy and Safety of Three Antiretroviral Regimens for Initial Treatment of HIV-1: A Randomized Clinical Trial in Diverse Multinational Settings
title_full Efficacy and Safety of Three Antiretroviral Regimens for Initial Treatment of HIV-1: A Randomized Clinical Trial in Diverse Multinational Settings
title_fullStr Efficacy and Safety of Three Antiretroviral Regimens for Initial Treatment of HIV-1: A Randomized Clinical Trial in Diverse Multinational Settings
title_full_unstemmed Efficacy and Safety of Three Antiretroviral Regimens for Initial Treatment of HIV-1: A Randomized Clinical Trial in Diverse Multinational Settings
title_sort efficacy and safety of three antiretroviral regimens for initial treatment of hiv-1: a randomized clinical trial in diverse multinational settings
publishDate 2018
url https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=84865566725&origin=inward
http://cmuir.cmu.ac.th/jspui/handle/6653943832/51864
_version_ 1681423846749503488
spelling th-cmuir.6653943832-518642018-09-04T06:10:46Z Efficacy and Safety of Three Antiretroviral Regimens for Initial Treatment of HIV-1: A Randomized Clinical Trial in Diverse Multinational Settings 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 Medicine 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:http://www.ClinicalTrials.gov NCT00084136. © 2012. 2018-09-04T06:10:46Z 2018-09-04T06:10:46Z 2012-08-01 Journal 15491676 15491277 2-s2.0-84865566725 10.1371/journal.pmed.1001290 https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=84865566725&origin=inward http://cmuir.cmu.ac.th/jspui/handle/6653943832/51864