Human immunodeficiency virus treatment-induced adipose tissue pathology and lipoatrophy: prevalence and metabolic consequences.

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.