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dc.contributor.authorCampbell, Thomas B.
dc.contributor.authorSmeaton, Laura Marie
dc.contributor.authorKumarasamy, N.
dc.contributor.authorFlanigan, Timothy
dc.contributor.authorKlingman, Karin L.
dc.contributor.authorFirnhaber, Cynthia
dc.contributor.authorGrinsztejn, Beatriz
dc.contributor.authorHosseinipour, Mina C.
dc.contributor.authorKumwenda, Johnstone
dc.contributor.authorLalloo, Umesh
dc.contributor.authorRiviere, Cynthia
dc.contributor.authorSanchez, Jorge
dc.contributor.authorMelo, Marineide
dc.contributor.authorSupparatpinyo, Khuanchai
dc.contributor.authorTripathy, Srikanth
dc.contributor.authorMartinez, Ana I.
dc.contributor.authorNair, Apsara
dc.contributor.authorWalawander, Ann
dc.contributor.authorMoran, Laura
dc.contributor.authorChen, Yun
dc.contributor.authorSnowden, Wendy
dc.contributor.authorRooney, James F.
dc.contributor.authorUy, Jonathan
dc.contributor.authorSchooley, Robert T.
dc.contributor.authorDe Gruttola, Victor Gerard
dc.contributor.authorHakim, James Gita
dc.date.accessioned2013-04-18T19:39:51Z
dc.date.issued2012
dc.identifier.citationCampbell, Thomas B., Laura M. Smeaton, N. Kumarasamy, Timothy Flanigan, Karin L. Klingman, Cynthia Firnhaber, Beatriz Grinsztejn, et al. 2012. Efficacy and safety of three antiretroviral regimens for initial treatment of HIV-1: a randomized clinical trial in diverse multinational settings. PLoS Medicine 9(8): e1001290.en_US
dc.identifier.issn1549-1277en_US
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:10579036
dc.description.abstractBackground: 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.en_US
dc.language.isoen_USen_US
dc.publisherPublic Library of Scienceen_US
dc.relation.isversionofdoi:10.1371/journal.pmed.1001290en_US
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3419182/pdf/en_US
dash.licenseLAA
dc.titleEfficacy and Safety of Three Antiretroviral Regimens for Initial Treatment of HIV-1: A Randomized Clinical Trial in Diverse Multinational Settingsen_US
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden_US
dc.relation.journalPLoS Medicineen_US
dash.depositing.authorDe Gruttola, Victor Gerard
dc.date.available2013-04-18T19:39:51Z
dc.identifier.doi10.1371/journal.pmed.1001290*
dash.authorsorderedfalse
dash.contributor.affiliatedSmeaton, Laura
dash.contributor.affiliatedDeGruttola, Victor


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