title: Peripheral and central fat changes in subjects randomized to abacavir-lamivudine or tenofovir-emtricitabine with atazanavir-ritonavir or efavirenz: ACTG Study A5224s.
abstract: BACKGROUND
  We compare the effect of 4 different antiretroviral regimens on limb and visceral fat.
  
  
  METHODS
  A5224s 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.
  
  
  RESULTS
  A5224s 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.
  
  
  CONCLUSIONS
  ABC-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.
  
  
  BACKGROUND
  NCT00118898.
authors.affiliation: Department of Pediatrics and Medicine, Case Western Reserve University and Rainbow Babies and Children's Hospital, Cleveland, Ohio 44106, USA. grace.mccomsey@case.edu
authors.forename: Grace A
authors.initials: GA
authors.lastname: McComsey
authors.forename: Douglas
authors.initials: D
authors.lastname: Kitch
authors.forename: Paul E
authors.initials: PE
authors.lastname: Sax
authors.forename: Pablo
authors.initials: P
authors.lastname: Tebas
authors.forename: Camlin
authors.initials: C
authors.lastname: Tierney
authors.forename: Nasreen C
authors.initials: NC
authors.lastname: Jahed
authors.forename: Laurie
authors.initials: L
authors.lastname: Myers
authors.forename: Kathleen
authors.initials: K
authors.lastname: Melbourne
authors.forename: Belinda
authors.initials: B
authors.lastname: Ha
authors.forename: Eric S
authors.initials: ES
authors.lastname: Daar
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000009:adverse effects*; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects* / Q000379:methods*; D050218:Body Fat Distribution; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1 / Q000302:isolation & purification; D039682:HIV-Associated Lipodystrophy Syndrome / Q000139:chemically induced*; D006801:Humans; D008297:Male; D008875:Middle Aged
chemical_list: D019380:Anti-HIV Agents