title: Human immunodeficiency virus treatment-induced adipose tissue pathology and lipoatrophy: prevalence and metabolic consequences.
abstract: BACKGROUND
  Lipoatrophy and metabolic complications of treatment of human immunodeficiency virus (HIV) infection may share common associations with adipose tissue pathology and inflammation. To investigate these relationships, we undertook a large-scale study of adipose tissue, body composition, and metabolic outcomes among HIV-infected adult men at a tertiary hospital HIV cohort during the period 2001-2007.
  
  
  METHODS
  Assessments included adipose biopsies (n = 211) for investigation of adipocyte mitochondrial DNA content, adipocytokine expression, and adipose macrophage content; and whole-body dual-energy x-ray absorptiometry (DEXA) scans (n = 225) for objective body composition changes; 138 individuals contributed both biopsy and DEXA data.
  
  
  RESULTS
  Compared with 78 treatment-naive control subjects, 98 zidovudine recipients (48%) and 49 stavudine recipients (67%) had leg fat measures <10% threshold value. Adipose samples associated with current stavudine or zidovudine (n = 99) revealed significant adipocyte mitochondrial DNA depletion, adipose tissue macrophage infiltration, and elevated proinflammatory cytokine levels, compared with samples from control subjects and nonthymidine nucleoside reverse-transcriptase inhibitor (NRTI) recipients (all P < .05). Improvements in adipose pathology after NRTI switching (n = 21 longitudinal samples) correlated with increased preswitch adipose inflammation and less severe fat loss (both P < .05). Elevated ratios of total to high-density lipoprotein cholesterol levels and Homeostatic Metabolic Assessment scores correlated independently with lipoatrophy severity (P < .05) and increased body mass index (P < .05) in thymidine NRTI-experienced individuals. No effect of demographic or HIV-related variables, or HIV protease inhibitor therapy exposure was detected.
  
  
  CONCLUSIONS
  Adipose tissue pathology and lipoatrophic fat loss are highly prevalent among recipients of stavudine- or zidovudine-based HIV treatment and are associated with adverse metabolic outcomes. Restoring adipose tissue health appears to be an important issue in the long-term treatment of this patient population.
authors.affiliation: Centre for Clinical Immunology and Biomedical Statistics, Royal Perth Hospital and Murdoch University, Perth, Western Australia.
authors.forename: Emma
authors.initials: E
authors.lastname: Hammond
authors.forename: Elizabeth
authors.initials: E
authors.lastname: McKinnon
authors.forename: David
authors.initials: D
authors.lastname: Nolan
mesh_terms: D052242:Adiponectin / Q000235:genetics / Q000378:metabolism; D000273:Adipose Tissue / Q000187:drug effects* / Q000473:pathology; D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000145:classification / Q000627:therapeutic use*; D001823:Body Composition; D016022:Case-Control Studies; D004272:DNA, Mitochondrial; D005786:Gene Expression Regulation; D015658:HIV Infections / Q000188:drug therapy*; D039682:HIV-Associated Lipodystrophy Syndrome / Q000139:chemically induced* / Q000453:epidemiology; D006801:Humans; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism; D020738:Leptin / Q000235:genetics / Q000378:metabolism; D008264:Macrophages; D008297:Male; D008875:Middle Aged; D015995:Prevalence
chemical_list: D052242:Adiponectin; D019380:Anti-HIV Agents; D004272:DNA, Mitochondrial; D016209:Interleukin-8; D020738:Leptin