title: Longer prior exposure to zidovudine/lamivudine-containing combination antiretroviral therapy, age, and male gender are each associated with reduced subcutaneous adipose tissue.
abstract: OBJECTIVE
  Whether zidovudine (AZT)-associated lipoatrophy occurrence differs by concomitant exposure to protease (PIs) or non-nucleoside reverse transcriptase inhibitors (NNRTIs) remains unclear. Baseline body composition data from a randomized trial in subjects stable on first-line AZT-based therapy were used to explore this issue.
  
  
  METHODS
  In this substudy of the PREPARE trial, centrally read baseline whole-body dual energy x-ray aborptiometry (DXA) and single-slice abdominal CT scans were analyzed with respect to duration and type of prior AZT/lamivudine (3TC) combination antiretroviral therapy (cART), including by multivariate linear regression adjusted for age, gender, ethnicity, body mass index (BMI), and nadir CD4.
  
  
  RESULTS
  DXA and CT, from 134 and 136 patients, respectively [87% male; 82% Caucasian; mean (SD) age, 45.6 years (10); BMI, 24.3 kg/m² (3.2)], were analyzed. Prior AZT/3TC cART exposure was 5.5 (2.2) years. Seventy-eight and 27 patients had concomitantly and exclusively used NNRTIs and PIs, respectively. AZT/3TC cART, AZT/3TC/NNRTI, and AZT/3TC/PI, respectively, were associated with the presence of a mean (95% CI) of 247 g (-438 to -56; P = .012), 267 g (-467 to -66; P = .010), and 216 g (-430 to -1.7; P = .048) less baseline limb fat per additional year of prior exposure. Although abdominal subcutaneous (SAT) adipose tissue was likewise less with longer AZT/3TC cART, this was only significant for AZT/3TC/ NNRTI but not AZT/3TC/PI. Visceral adipose tissue (VAT) amount was not clearly associated to prior treatment. Increased age and male gender were independently associated with lower limb fat and SAT, but more VAT.
  
  
  CONCLUSIONS
  Longer exposure to AZT/3TC, regardless of whether in combination with PI or NNRTI, as well as increased age and male gender are independently associated with lower limb fat mass.
authors.affiliation: Department of Global Health, Amsterdam Institute for Global Health and Development, Amsterdam, The Netherlands. Saskia.Vrouenraets@siz.nl
authors.forename: S M E
authors.initials: SM
authors.lastname: Vrouenraets
authors.forename: F W N M
authors.initials: FW
authors.lastname: Wit
authors.forename: E Fernandez
authors.initials: EF
authors.lastname: Garcia
authors.forename: M
authors.initials: M
authors.lastname: Huber
authors.forename: K
authors.initials: K
authors.lastname: Brinkman
authors.forename: G
authors.initials: G
authors.lastname: Moyle
authors.forename: P
authors.initials: P
authors.lastname: Domingo
authors.forename: P E
authors.initials: PE
authors.lastname: Tarr
authors.forename: D
authors.initials: D
authors.lastname: Podzamczer
authors.forename: M
authors.initials: M
authors.lastname: Ristola
authors.forename: J M
authors.initials: JM
authors.lastname: Gatell
authors.forename: J M
authors.initials: JM
authors.lastname: Livrozet
authors.forename: H
authors.initials: H
authors.lastname: Furrer
authors.forename: P
authors.initials: P
authors.lastname: Reiss
mesh_terms: D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D001823:Body Composition / Q000187:drug effects; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy*; D006801:Humans; D019259:Lamivudine / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use*; D008297:Male; D050151:Subcutaneous Fat / Q000187:drug effects*; D015215:Zidovudine / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use*
chemical_list: D019380:Anti-HIV Agents; D019259:Lamivudine; D015215:Zidovudine