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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 are...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3419182/ https://www.ncbi.nlm.nih.gov/pubmed/22936892 http://dx.doi.org/10.1371/journal.pmed.1001290 |
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author | 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 |
author_facet | 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 |
author_sort | Campbell, Thomas B. |
collection | PubMed |
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: www.ClinicalTrials.gov NCT00084136 Please see later in the article for the Editors' Summary. |
format | Online Article Text |
id | pubmed-3419182 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-34191822012-08-30 Efficacy and Safety of Three Antiretroviral Regimens for Initial Treatment of HIV-1: A Randomized Clinical Trial in Diverse Multinational Settings 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 PLoS Med Research Article 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. Public Library of Science 2012-08-14 /pmc/articles/PMC3419182/ /pubmed/22936892 http://dx.doi.org/10.1371/journal.pmed.1001290 Text en https://creativecommons.org/publicdomain/zero/1.0/ This is an open-access article distributed under the terms of the Creative Commons Public Domain declaration, which stipulates that, once placed in the public domain, this work may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. |
spellingShingle | Research Article 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 Efficacy and Safety of Three Antiretroviral Regimens for Initial Treatment of HIV-1: A Randomized Clinical Trial in Diverse Multinational Settings |
title | 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_short | 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 |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3419182/ https://www.ncbi.nlm.nih.gov/pubmed/22936892 http://dx.doi.org/10.1371/journal.pmed.1001290 |
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