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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
- Source :
- PLoS medicine, vol 9, iss 8, PLoS Medicine, Vol 9, Iss 8, p e1001290 (2012)
- Publication Year :
- 2012
- Publisher :
- Public Library of Science (PLoS), 2012.
-
Abstract
- BackgroundAntiretroviral 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 findings1,571 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; pConclusionEFV+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 registrationwww.ClinicalTrials.gov NCT00084136. Please see later in the article for the Editors' Summary.
- Subjects :
- Male
Comparative Effectiveness Research
Time Factors
Internationality
HIV Infections
Medical and Health Sciences
law.invention
chemistry.chemical_compound
0302 clinical medicine
Randomized controlled trial
Pregnancy
law
030212 general & internal medicine
0303 health sciences
education.field_of_study
Coinfection
Hazard ratio
virus diseases
General Medicine
3. Good health
Infectious Diseases
Treatment Outcome
6.1 Pharmaceuticals
Combination
HIV/AIDS
Medicine
Female
Patient Safety
Infection
medicine.drug
medicine.medical_specialty
Efavirenz
Anti-HIV Agents
Clinical Trials and Supportive Activities
Population
Antiretroviral Therapy
Emtricitabine
03 medical and health sciences
Drug Therapy
Clinical Research
General & Internal Medicine
Internal medicine
PEARLS study team of the ACTG
medicine
Humans
Highly Active
Dosing
education
030306 microbiology
business.industry
Evaluation of treatments and therapeutic interventions
Mycobacterium tuberculosis
Surgery
Atazanavir
Regimen
Withholding Treatment
chemistry
HIV-1
business
Follow-Up Studies
Subjects
Details
- ISSN :
- 15491676
- Volume :
- 9
- Database :
- OpenAIRE
- Journal :
- PLoS Medicine
- Accession number :
- edsair.doi.dedup.....f39735b2debbf1fd5c17fbe4527a08eb