title: Impact of randomized antiretroviral therapy initiation on glucose metabolism.
abstract: OBJECTIVE
  Prior studies have found that early HIV protease inhibitors contribute to glucose dysregulation. Few randomized trials have evaluated glucose indices in antiretroviral-naive individuals on newer antiretroviral therapy (ART).
  
  
  METHODS
  A5224s was a substudy of A5202, a prospective trial of 1857 ART-naive participants randomized to blinded abacavir-lamivudine (ABC/3TC) or tenofovir DF-emtricitabine (TDF/FTC) with open-label efavirenz (EFV) or atazanavir-ritonavir (ATV/r). Analyses used two-sample t-tests, Spearman correlation coefficients and linear regression.
  
  
  RESULTS
  A5224s included 269 nondiabetic individuals: 85% men, 47% white non-Hispanic, baseline median age 38 years, HIV-1 RNA 4.6 log10 copies/ml and CD4 cell count 233 cells/μl. Overall, significant 96-week increases occurred in fasting glucose, insulin and the homeostatic model assessment of insulin resistance (HOMA-IR), P ≤ 0.004. Assignment to EFV (versus ATV/r) resulted in significantly greater glucose increase [mean difference 4.4; 95% confidence interval (CI) 1.3, 7.5 mg/dl; P = 0.006] but not insulin or HOMA-IR (P ≥ 0.72). Glucose indices were not significantly different between ABC/3TC and TDF/FTC arms, P ≥ 0.18. Significant correlations were detected between changes in glucose indices and changes in BMI; all r ≥ 0.23, P ≤ 0.001. In multivariable analyses, in addition to the EFV effect, higher baseline HIV-1 RNA and greater BMI change were significant independent factors associated with greater glucose increase.
  
  
  CONCLUSIONS
  Changes in glucose metabolism were not significantly different between TDF/FTC and ABC/3TC-based regimens. A small but significantly greater increase in glucose was observed in those assigned to EFV. As glucose dysregulation may increase with time on ART, longer term studies will be needed to further clarify the clinical significance of these findings.
authors.affiliation: aUniversity of Colorado-Anschutz Medical Campus, Aurora, Colorado bHarvard School of Public Health cBrigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts dLos Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance eGilead Sciences, Foster City, California fViiV Healthcare, Research Triangle, North Carolina gCase Western Reserve University, Cleveland, Ohio, USA.
authors.forename: Kristine Mace
authors.initials: KM
authors.lastname: Erlandson
authors.forename: Douglas
authors.initials: D
authors.lastname: Kitch
authors.forename: Camlin
authors.initials: C
authors.lastname: Tierney
authors.forename: Paul E
authors.initials: PE
authors.lastname: Sax
authors.forename: Eric S
authors.initials: ES
authors.lastname: Daar
authors.forename: Kathleen M
authors.initials: KM
authors.lastname: Melbourne
authors.forename: Belinda
authors.initials: B
authors.lastname: Ha
authors.forename: Grace A
authors.initials: GA
authors.lastname: McComsey
mesh_terms: D000293:Adolescent; D000328:Adult; D019380:Anti-HIV Agents / Q000009:adverse effects* / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects* / Q000379:methods*; D001786:Blood Glucose / Q000032:analysis*; D004311:Double-Blind Method; D004734:Energy Metabolism / Q000187:drug effects*; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D008297:Male; D011446:Prospective Studies; D055815:Young Adult
chemical_list: D019380:Anti-HIV Agents; D001786:Blood Glucose