Efficacy and safety of three antiretroviral regimens for initial treatment of HIV-1: a randomized clinical trial in diverse multinational settings.
<h4>Background</h4>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 do...
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2012
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oai:doaj.org-article:28bce7526ebb4cd2809cf9e8b4bd1e1a2021-11-18T05:42:08ZEfficacy and safety of three antiretroviral regimens for initial treatment of HIV-1: a randomized clinical trial in diverse multinational settings.1549-12771549-167610.1371/journal.pmed.1001290https://doaj.org/article/28bce7526ebb4cd2809cf9e8b4bd1e1a2012-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pmed.1001290https://doaj.org/toc/1549-1277https://doaj.org/toc/1549-1676<h4>Background</h4>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.<h4>Methods and findings</h4>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).<h4>Conclusion</h4>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.<h4>Trial registration</h4>www.ClinicalTrials.gov NCT00084136. Please see later in the article for the Editors' Summary.Thomas B CampbellLaura M SmeatonN KumarasamyTimothy FlaniganKarin L KlingmanCynthia FirnhaberBeatriz GrinsztejnMina C HosseinipourJohnstone KumwendaUmesh LallooCynthia RiviereJorge SanchezMarineide MeloKhuanchai SupparatpinyoSrikanth TripathyAna I MartinezApsara NairAnn WalawanderLaura MoranYun ChenWendy SnowdenJames F RooneyJonathan UyRobert T SchooleyVictor De GruttolaJames Gita HakimPEARLS study team of the ACTGPublic Library of Science (PLoS)articleMedicineRENPLoS Medicine, Vol 9, Iss 8, p e1001290 (2012) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
Medicine R |
| spellingShingle |
Medicine R 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 PEARLS study team of the ACTG Efficacy and safety of three antiretroviral regimens for initial treatment of HIV-1: a randomized clinical trial in diverse multinational settings. |
| description |
<h4>Background</h4>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.<h4>Methods and findings</h4>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).<h4>Conclusion</h4>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.<h4>Trial registration</h4>www.ClinicalTrials.gov NCT00084136. Please see later in the article for the Editors' Summary. |
| format |
article |
| 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 PEARLS study team of the ACTG |
| 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 PEARLS study team of the ACTG |
| 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. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2012 |
| url |
https://doaj.org/article/28bce7526ebb4cd2809cf9e8b4bd1e1a |
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