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Predictors of limb fat gain in HIV positive patients following a change to tenofovir-emtricitabine or abacavir-lamivudine.

ABSTRACT: Antiretroviral treatment (cART) in HIV causes lipoatrophy. We examined predictors of anthropometric outcomes over 96 weeks in HIV-infected, lipoatrophic adults receiving stable cART randomised to tenofovir-emtricitabine (TDF-FTC) or abacavir-lamivudine (ABC-3TC) fixed dose combinations.The STEAL study was a prospective trial of virologically suppressed participants randomised to either TDF-FTC (n = 178) or ABC-3TC (n = 179). Anthropometric assessment was conducted at baseline, weeks 48 and 96. The analysis population included those with baseline and week 96 data remaining on randomised therapy. Distribution of limb fat change was divided into four categories (? 0%, >0-10%, >10-20%, >20%). Baseline characteristics [demographics, medical history, metabolic and cardiovascular biomarkers] were assessed as potential predictors of change in percent subcutaneous limb fat using linear regression. 303 participants (85% of STEAL population) were included. Baseline characteristics were: mean (± SD) age 45 (± 8) years; thymidine analogue nucleoside reverse transcriptase inhibitor (tNRTI) duration 4 (± 3) years; limb fat 5.4 (± 3.0)kg; body mass index 24.7 (± 3 .5) kg/m(2). Mean (SD) limb fat gain to week 48 and 96 was 7.6% (± 22.4) and 13.2% (± 27.3), respectively, with no significant difference between groups. 51.5% of all participants had >10% gain in limb fat. Predictors of greater limb fat gain at week 96 were baseline tNRTI (10.3, p = 0.001), glucose >6 mmol/L (16.1, p = 0.04), higher interleukin 6 (IL-6) (2.8, p = 0.004) and lower baseline limb fat (3.8-6.4 kg - 11.2; >6.4 kg - 15.7, p trend<0.001).Modest peripheral fat gain occurred with both TDF-FTC and ABC-3TC. Baseline factors associated with more severe lipodystrophy (lipoatrophy, baseline tNRTI, raised IL6, and glucose) predicted greater limb fat recovery at 96 weeks.

SUBMITTER: Martin A

PROVIDER: S-EPMC3203920 | biostudies-literature | 2011

REPOSITORIES: biostudies-literature

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Predictors of limb fat gain in HIV positive patients following a change to tenofovir-emtricitabine or abacavir-lamivudine.

Martin Allison A Amin Janaki J Emery Sean S Baker David D Carr Andrew A Cooper David A DA Bloch Mark M

PloS one 20111028 10

<h4>Background</h4>Antiretroviral treatment (cART) in HIV causes lipoatrophy. We examined predictors of anthropometric outcomes over 96 weeks in HIV-infected, lipoatrophic adults receiving stable cART randomised to tenofovir-emtricitabine (TDF-FTC) or abacavir-lamivudine (ABC-3TC) fixed dose combinations.<h4>Methodology/principal findings</h4>The STEAL study was a prospective trial of virologically suppressed participants randomised to either TDF-FTC (n = 178) or ABC-3TC (n = 179). Anthropometri ...[more]

PMID: 22046394

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Project description:BackgroundThe use of fixed-dose combination nucleoside reverse-transcriptase inhibitors (NRTIs) with a nonnucleoside reverse-transcriptase inhibitor or a ritonavir-boosted protease inhibitor is recommended as initial therapy in patients with human immunodeficiency virus type 1 (HIV-1) infection, but which NRTI combination has greater efficacy and safety is not known.MethodsIn a randomized, blinded equivalence study involving 1858 eligible patients, we compared four once-daily antiretroviral regimens as initial therapy for HIV-1 infection: abacavir-lamivudine or tenofovir disoproxil fumarate (DF)-emtricitabine plus efavirenz or ritonavir-boosted atazanavir. The primary efficacy end point was the time from randomization to virologic failure (defined as a confirmed HIV-1 RNA level > or = 1000 copies per milliliter at or after 16 weeks and before 24 weeks, or > or = 200 copies per milliliter at or after 24 weeks).ResultsA scheduled interim review by an independent data and safety monitoring board showed significant differences in virologic efficacy, according to the NRTI combination, among patients with screening HIV-1 RNA levels of 100,000 copies per milliliter or more. At a median follow-up of 60 weeks, among the 797 patients with screening HIV-1 RNA levels of 100,000 copies per milliliter or more, the time to virologic failure was significantly shorter in the abacavir-lamivudine group than in the tenofovir DF-emtricitabine group (hazard ratio, 2.33; 95% confidence interval, 1.46 to 3.72; P<0.001), with 57 virologic failures (14%) in the abacavir-lamivudine group versus 26 (7%) in the tenofovir DF-emtricitabine group. The time to the first adverse event was also shorter in the abacavir-lamivudine group (P<0.001). There was no significant difference between the study groups in the change from the baseline CD4 cell count at week 48.ConclusionsIn patients with screening HIV-1 RNA levels of 100,000 copies per milliliter or more, the times to virologic failure and the first adverse event were both significantly shorter in patients randomly assigned to abacavir-lamivudine than in those assigned to tenofovir DF-emtricitabine. (ClinicalTrials.gov number, NCT00118898.)

Project description:BackgroundWe compare the effect of 4 different antiretroviral regimens on limb and visceral fat.MethodsA5224s was a substudy of A5202, a trial of human immunodeficiency virus type 1 (HIV-1)-infected, treatment-naive subjects randomized to blinded abacavir-lamivudine (ABC-3TC) or tenofovir DF-emtricitabine (TDF-FTC) with open-label efavirenz (EFV) or atazanavir-ritonavir (ATV-r). The primary endpoint was the presence of lipoatrophy (≥ 10% loss of limb fat) at week 96 by intent-to-treat (ITT) analysis. Secondary endpoints included changes in limb and visceral fat. Statistical tests included linear regression, binomial, two-sample t test, and Fisher's exact test.ResultsA5224s enrolled 269 subjects; 85% were male, and 47% were white non-Hispanic. The subjects had a median baseline HIV-1 RNA level of 4.6 log(10) copies/mL, a median age of 38 years, a median CD4+ cell count of 233 cells/μL, median limb fat of 7.4 kg, median visceral adipose tissue (VAT) of 84.1 cm(2), and VAT: total adipose tissue (TAT) ratio of 0.31. At week 96, estimated prevalence of lipoatrophy (upper 95% confidence interval [CI]) was 18% (25%) for ABC-3TC and 15% (22%) for TDF-FTC (P = .70); this was not significantly less than the hypothesized 15% for both (P ≥ .55 for both). The secondary as-treated (AT) analysis showed similar results. At week 96, the estimated mean percentage change from baseline in VAT was higher for the ATV-r group than for the EFV group (26.6% vs 12.4%; P = .090 in ITT analysis and 30.0% vs 14.5%; P = .10 in AT analysis); however, the percentage change in VAT:TAT was similar by ITT and AT analysis (P ≥ .60 for both). Results were similar for absolute changes in VAT and VAT:TAT.ConclusionsABC-3TC- and TDF-FTC-based regimens increased limb and visceral fat at week 96, with a similar prevalence of lipoatrophy. Compared to the EFV group, subjects assigned to ATV-r had a trend towards higher mean percentage increase in VAT.Clinical trials registrationNCT00118898.

Project description:BackgroundTherapy with tenofovir is associated with lower bone mineral density (BMD), higher markers of bone turnover and increased fracture risk in HIV-infected adults. Bone structural parameters generated by hip structural analysis may represent a separate measure of bone strength, but have not been assessed in HIV.MethodsDual-energy X-ray absorptiometry (DXA) scans from 254 HIV-infected adults randomised to simplify their existing dual nucleoside analogue reverse transcriptase inhibitor therapy to coformulated tenofovir-emtricitabine or abacavir-lamivudine were analysed using DXA-derived hip structural analysis software. Hip structural parameters included femoral strength index, section modulus, cross-sectional area, and cross-sectional moment of inertia. We used one-way ANOVA to test the relationship between nucleoside analogue type at baseline and structural parameters, multivariable analysis to assess baseline covariates associated with femoral strength index, and t-tests to compare mean change in structural parameters over 96 weeks between randomised groups.ResultsParticipants taking tenofovir at baseline had lower section modulus (-107.3 mm2, p = 0.001), lower cross-sectional area (-15.01 mm3, p = 0.001), and lower cross-sectional moment of inertia (-2,036.8 mm4, p = 0.007) than those receiving other nucleoside analogues. After adjustment for baseline risk factors, the association remained significant for section modulus (p = 0.008) and cross-sectional area (p = 0.002). Baseline covariates significantly associated with higher femoral strength index were higher spine T-score (p = 0.001), lower body fat mass (p<0.001), lower bone alkaline phosphatase (p = 0.025), and higher osteoprotegerin (p = 0.024). Hip structural parameters did not change significantly over 96 weeks and none was significantly affected by treatment simplification to tenofovir-emtricitabine or abacavir-lamivudine.ConclusionIn this population, tenofovir use was associated with reduced composite indices of bone strength as measured by hip structural analysis, but none of the structural parameters improved significantly over 96 weeks with tenofovir cessation.Trial registrationClinicalTrials.gov NCT00192634.

Project description:BackgroundDespite evidence shown of dolutegravir (DTG)-related neurotoxicity, which may be more common when combined with abacavir (ABC), its reversibility has not been explored in a clinical trial.MethodsWe conducted a randomized, multicenter, open-label, pilot trial to evaluate the reversibility of patient-reported neuropsychiatric symptoms, developed or worsened on DTG/ABC/lamivudine (DTG/ABC/3TC), in virologically suppressed patients switched to cobicistat-boosted-elvitegravir/emtricitabine/tenofovir-alafenamide (EVG/COBI/FTC/TAF). Participants were randomized to immediate switch (baseline) or to defer switch (week 4), and then all completed 24 weeks of follow up on EVG/COBI/FTC/TAF. At each visit, participants completed Pittsburgh Sleep Quality Index (PSQI) and Hospital Anxiety and Depression (HAD) scales and were interviewed about 11 neuropsychiatric symptoms potentially related with DTG through a questionnaire. At baseline and at the end of follow up, they also performed neurocognitive testing. Our primary objective was to compare changes in neuropsychiatric symptoms and PSQI and HAD scales between arms at week 4. Secondary objectives were to evaluate changes in neuropsychiatric symptoms and PSQI and HAD scales at weeks 4, 12, and 24 after switching to EVG/COBI/FTC/TAF and in neurocognitive performance and magnetic resonance imaging biomarkers at end of follow up.ResultsThirty-eight participants were included. Study arms were similar at baseline. At week 4, neuropsychiatric symptoms and PSQI and HAD scores remained unchanged in participants receiving DTG/ABC/3TC and improved significantly in participants receiving EVG/COBI/FTC/TAF. These significant improvements were also observed at weeks 4, 12, and 24 after all participants switched to EVG/COBI/FTC/TAF. In addition, global neurocognitive performance improved (NPZ-7) after switching to EVG/COBI/FTC/TAF.ConclusionsNeuropsychiatric symptoms in patients on DTG/ABC/3TC could resolve or improve after switching to EVG/COBI/FTC/TAF.

Dataset Information

Predictors of limb fat gain in HIV positive patients following a change to tenofovir-emtricitabine or abacavir-lamivudine.

Publications

Predictors of limb fat gain in HIV positive patients following a change to tenofovir-emtricitabine or abacavir-lamivudine.

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