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A Randomized Comparison of Anthropomorphic Changes With Preferred and Alternative Efavirenz-Based Antiretroviral Regimens in Diverse Multinational Settings.

ABSTRACT: Background. ?Existing data on anthropomorphic changes in resource-limited settings primarily come from observational or cross-sectional studies. Data from randomized clinical trials are needed to inform treatment decisions in these areas of the world. Methods. ?The AIDS Clinical Trials Group Prospective Evaluation of Antiretrovirals in Resource-Limited Settings (PEARLS) study was a prospective, randomized evaluation of the efficacy of emtricitabine/tenofovir + efavirenz (FTC/TDF + EFV) vs lamivudine/zidovudine + efavirenz (3TC/ZDV + EFV) for the initial treatment of human immunodeficiency virus (HIV)-1-infected individuals from resource-diverse settings. Changes in anthropomorphic measures were analyzed using mixed-effect models for repeated measurements, using all available measurements at weeks 48, 96, and 144. Intent-to-treat results are presented; as-treated results were similar. Results. ?Five hundred twenty-six participants were randomized to FTC/TDF + EFV, and 519 participants were randomized to 3TC/ZDV + EFV. Significantly greater increases from baseline to week 144 were seen among those randomized to FTC/TDF + EFV vs 3TC/ZDV + EFV in all measures except waist-to-hip ratio, with the following mean changes: weight, 4.8 vs 3.0 kg; body mass index, 1.8 vs 1.1 kg/m(2); mid-arm, 1.7 vs 0.7 cm; waist, 5.2 vs 4.3 cm; hip, 3.8 vs 1.4 cm; and mid-thigh circumference, 3.1 vs 0.9 cm. There were 7 clinical diagnoses of lipoatrophy in the 3TC/ZDV + EFV arm compared with none in the FTC/TDF + EFV arm. The proportion of overweight or obese participants increased from 25% (week 0) to 42% (week 144) for FTC/TDF + EFV and from 26% to 38% for 3TC/ZDV + EFV. Conclusions. ?Our findings support first-line use of FTC/TDF + EFV in resource-limited settings and emphasize the need for interventions to limit weight gain among overweight or obese HIV-infected participants in all settings.

SUBMITTER: Erlandson KM

PROVIDER: S-EPMC4512142 | biostudies-literature | 2015 Sep

REPOSITORIES: biostudies-literature

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A Randomized Comparison of Anthropomorphic Changes With Preferred and Alternative Efavirenz-Based Antiretroviral Regimens in Diverse Multinational Settings.

Erlandson Kristine M KM Taejaroenkul Sineenart S Smeaton Laura L Gupta Amita A Singini Isaac L IL Lama Javier R JR Mngqibisa Rosie R Firnhaber Cynthia C Cardoso Sandra Wagner SW Kanyama Cecilia C Machado da Silva Andre L AL Hakim James G JG Kumarasamy Nagalingeswaran N Campbell Thomas B TB Hughes Michael D MD

Open forum infectious diseases 20150624 3

Background. Existing data on anthropomorphic changes in resource-limited settings primarily come from observational or cross-sectional studies. Data from randomized clinical trials are needed to inform treatment decisions in these areas of the world. Methods. The AIDS Clinical Trials Group Prospective Evaluation of Antiretrovirals in Resource-Limited Settings (PEARLS) study was a prospective, randomized evaluation of the efficacy of emtricitabine/tenofovir + efavirenz (FTC/TDF + EFV) vs lamivu ...[more]

PMID: 26213694

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Project description: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; 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).ConclusionEFV+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.

Project description:ImportanceWorldwide, the nonnucleoside reverse transcriptase inhibitors (NNRTIs) efavirenz and nevirapine are commonly used in first-line antiretroviral regimens in both adults and children with human immunodeficiency virus (HIV) infection. Data on the comparative effectiveness of these medications in children are limited.ObjectiveTo investigate whether virological failure is more likely among children who initiated 1 or the other NNRTI-based HIV treatment.Design, setting, and participantsRetrospective cohort study of children (aged 3-16 years) who initiated efavirenz-based (n = 421) or nevirapine-based (n = 383) treatment between April 2002 and January 2011 at a large pediatric HIV care setting in Botswana.Main outcomes and measuresThe primary outcome was time from initiation of therapy to virological failure. Virological failure was defined as lack of plasma HIV RNA suppression to less than 400 copies/mL by 6 months or confirmed HIV RNA of 400 copies/mL or greater after suppression. Cox proportional hazards regression analysis compared time to virological failure by regimen. Multivariable Cox regression controlled for age, sex, baseline immunologic category, baseline clinical category, baseline viral load, nutritional status, NRTIs used, receipt of single-dose nevirapine, and treatment for tuberculosis.ResultsWith a median follow-up time of 69 months (range, 6-112 months; interquartile range, 23-87 months), 57 children (13.5%; 95% CI, 10.4%-17.2%) initiating treatment with efavirenz and 101 children (26.4%; 95% CI, 22.0%-31.1%) initiating treatment with nevirapine had virological failure. There were 11 children (2.6%; 95% CI, 1.3%-4.6%) receiving efavirenz and 20 children (5.2%; 95% CI, 3.2%-7.9%) receiving nevirapine who never achieved virological suppression. The Cox proportional hazard ratio for the combined virological failure end point was 2.0 (95% CI, 1.4-2.7; log rank P < .001, favoring efavirenz). None of the measured covariates affected the estimated hazard ratio in the multivariable analyses.Conclusions and relevanceAmong children aged 3 to 16 years infected with HIV and treated at a clinic in Botswana, the use of efavirenz compared with nevirapine as initial antiretroviral treatment was associated with less virological failure. These findings may warrant additional research evaluating the use of efavirenz and nevirapine for pediatric patients.

Project description:BackgroundAccording to World Health Organization (WHO) guidelines, which have also been adopted by the National AIDS Control Organization (NACO), India, Efavirenz-based Anti-Retroviral Therapy (ART) is better in Human-Immunodeficiency-Virus (HIV)-infected patients who are also being treated with Rifampicin-based Anti-Tuberculous Therapy (ATT). However, Efavirenz is much more expensive. We hypothesize that Nevirapine is a cheaper alternative that possesses equal efficacy as Efavirenz in HIV-Tuberculosis (TB) co-infected patients.MethodsA parallel open-label randomized clinical trial was conducted at All India Institute of Medical Sciences (AIIMS), New Delhi and National AIDS Research Institute (NARI), Pune. Those who were ART-naïve and co-infected with TB were randomized to receive either Nevirapine (Group 1)- or Efavirenz (Group 2)-based ART along with Rifampicin-based ATT. ATT was begun first in ART-naïve patients according to the NACO guidelines, with a median of 27 days between ATT and ART in both groups. The primary endpoint was a composite unfavourable outcome (death and/or ART failure) at 96 weeks, and the secondary outcome was successful TB treatment at 48 weeks.ResultsA total of 284 patients (mean age 36.7 ± 8.1 years) were randomized in a 1:1 ratio to receive either Nevirapine (n = 144)- or Efavirenz (n = 140)-based ART after a median ATT-ART gap of 27 days. The median CD4 count was 105 cells/μl, with a median viral load of 820,200 copies/μl and no significant difference between the groups. Composite unfavourable outcomes were reported in 49 patients in the Nevirapine group and 51 patients in the Efavirenz group (35.3% vs. 36.9%; hazard ratio, 0.95, 95% confidence interval (CI), 0.63,1.43, adjusted). There was no difference in successful TB treatment outcome between the groups (71.5% vs. 65.6%, 95% CI -3.8,17.9, adjusted). The results were similar, showing no difference between the groups in the two centres of the study after adjusting for disease stage.ConclusionsComposite unfavourable outcome in HIV-TB co-infected patients who were ART-naïve showed no statistically significant difference in the Nevirapine or Efavirenz groups.. Therefore, Nevirapine-based ART is a reasonable alternative to Efavirenz in resource-limited settings. However, multi-centric studies with larger sample sizes are required to confirm these findings.Trial registrationNCT01805258 (Retrospectively registered on March 6, 2013) Date of registration: March 2013.

Dataset Information

A Randomized Comparison of Anthropomorphic Changes With Preferred and Alternative Efavirenz-Based Antiretroviral Regimens in Diverse Multinational Settings.

Publications

A Randomized Comparison of Anthropomorphic Changes With Preferred and Alternative Efavirenz-Based Antiretroviral Regimens in Diverse Multinational Settings.

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