Dataset Information

Changes in Insulin Resistance After Initiation of Raltegravir or Protease Inhibitors With Tenofovir-Emtricitabine: AIDS Clinical Trials Group A5260s.

ABSTRACT: Background. ?Antiretroviral therapy (ART) can alter glucose metabolism, but little data exist on the association of raltegravir (RAL) with insulin resistance. Methods. ?A5260s was a substudy of A5257, a prospective open-label randomized trial in which human immunodeficiency virus (HIV)-infected treatment-naive participants were randomized to tenofovir-emtricitabine (TDF/FTC) plus atazanavir-ritonavir (ATV/r), darunavir-ritonavir (DRV/r), or RAL over 96 weeks. Baseline and changes in insulin resistance as estimated by the homeostatic model assessment of insulin resistance (HOMA-IR) were assessed. Wilcoxon rank-sum tests were used to assess shifts in the distribution of fold increase from baseline between treatment arms, and Spearman correlation was used to assess associations between HOMA-IR and measures of inflammation and body composition. Results. ?Three hundred twenty-eight participants were randomized; 90% were male, baseline median age was 36, HIV ribonucleic acid copies were 4.55 log10 copies/mL, and CD4 cell count was 349/mm3. Overall, HOMA-IR increased significantly after 4 weeks (1.9-fold change; 95% confidence interval, 1.73-2.05) then plateaued over the remainder of the study. Changes in HOMA-IR were not different between the arms (P ? .23). Changes in HOMA-IR were associated with changes in body mass index at weeks 48 and 96 (r = 0.12-0.22; P ? .04). There was a trend with increases in HOMA-IR and increases in visceral abdominal fat at week 96 (r = 0.12; P = .06). At 48 and 96 weeks, HOMA-IR correlated with interleukin-6, high-sensitivity C-reactive protein, and soluble CD163 (r = 0.16-0.27; P ? .003). Conclusions. ?Insulin resistance increased rapidly and then plateaued in treatment-naive participants initiating ART with TDF/FTC, and no differences were found with RAL when compared with ATV/r or DRV/r.

SUBMITTER: Dirajlal-Fargo S

PROVIDER: S-EPMC5047417 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature

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Changes in Insulin Resistance After Initiation of Raltegravir or Protease Inhibitors With Tenofovir-Emtricitabine: AIDS Clinical Trials Group A5260s.

Dirajlal-Fargo Sahera S Moser Carlee C Brown Todd T TT Kelesidis Theodoros T Dube Michael P MP Stein James H JH Currier Judith J McComsey Grace A GA

Open forum infectious diseases 20160829 3

Background. Antiretroviral therapy (ART) can alter glucose metabolism, but little data exist on the association of raltegravir (RAL) with insulin resistance. Methods. A5260s was a substudy of A5257, a prospective open-label randomized trial in which human immunodeficiency virus (HIV)-infected treatment-naive participants were randomized to tenofovir-emtricitabine (TDF/FTC) plus atazanavir-ritonavir (ATV/r), darunavir-ritonavir (DRV/r), or RAL over 96 weeks. Baseline ...[more]

PMID: 27704026

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Project description:AIDS Clinical Trial Group study A5202 (ClinicalTrials.gov identifier NCT00118898) was a phase 3b, randomized, partially blinded equivalence study of open-label atazanavir/ritonavir or efavirenz, plus either placebo-controlled tenofovir disoproxil fumarate/emtricitabine or abacavir/lamivudine, in treatment-naive adults living with HIV-1, evaluating efficacy, safety, and tolerability. We report an analysis of the contribution of participant characteristics to the disposition of tenofovir plasma concentrations. Tenofovir concentration data from a total of 817 individuals (88% of the total number of eligible patients randomly assigned to receive treatment in the TDF-containing arms of A5202) were available for analysis. Pharmacokinetic analysis was performed using nonlinear mixed-effects modeling. One- and two-compartment models with first-order absorption and first-order elimination were evaluated. An exponential error model was used for examination of interindividual variability (IIV), and a proportional and mixed-error model was assessed for residual variability. The final structural model contained two compartments with first-order absorption and elimination. IIV was estimated for apparent clearance (CL/F) and the first-order absorption rate constant (ka ), and a proportional residual variability model was selected. The final mean parameter estimates were as follows: ka = 2.87 h-1, CL/F = 37.2 liters/h, apparent volumes of the central and peripheral compartments = 127 and 646 liters, respectively, and apparent intercompartmental clearance = 107 liters/h. In addition to race/ethnicity, creatinine clearance and assignment to atazanavir/ritonavir or efavirenz were significantly associated with CL/F (P < 0.001). In conclusion, race/ethnicity is associated with tenofovir oral CL in HIV-1 positive, treatment-naive adults. This covariate relationship raises questions about the possibility of differences in efficacy and risk of adverse events in different patient populations and suggests that examining preexposure prophylaxis regimens and tenofovir exposure in different race/ethnicity groups be considered.

Dataset Information

Changes in Insulin Resistance After Initiation of Raltegravir or Protease Inhibitors With Tenofovir-Emtricitabine: AIDS Clinical Trials Group A5260s.

Publications

Changes in Insulin Resistance After Initiation of Raltegravir or Protease Inhibitors With Tenofovir-Emtricitabine: AIDS Clinical Trials Group A5260s.

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