title: 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 log10copies/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.
authors.affiliation: Department of Pediatric/Infectious Diseases and Rheumatology , Case Western Reserve University , Cleveland, Ohio.
authors.forename: Sahera
authors.initials: S
authors.lastname: Dirajlal-Fargo
authors.affiliation: Harvard School of Public Health, Boston, Massachusetts.
authors.forename: Carlee
authors.initials: C
authors.lastname: Moser
authors.affiliation: Department of Medicine/Endocrinology and Metabolism , Johns Hopkins University , Baltimore, Maryland.
authors.forename: Todd T
authors.initials: TT
authors.lastname: Brown
authors.affiliation: Department of Medicine/Infectious Diseases , UCLA , Los Angeles, California.
authors.forename: Theodoros
authors.initials: T
authors.lastname: Kelesidis
authors.affiliation: Department of Medicine , University of Southern California Keck School of Medicine , Los Angeles.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Dube
authors.affiliation: Department of Medicine , University of Wisconsin School of Medicine and Public Health , Madison.
authors.forename: James H
authors.initials: JH
authors.lastname: Stein
authors.affiliation: Department of Medicine/Infectious Diseases , UCLA , Los Angeles, California.
authors.forename: Judith
authors.initials: J
authors.lastname: Currier
authors.affiliation: Department of Pediatric/Infectious Diseases and Rheumatology , Case Western Reserve University , Cleveland, Ohio.
authors.forename: Grace A
authors.initials: GA
authors.lastname: McComsey
keywords: inflammatory markers; insulin resistance; raltegravir