Journal Article

Human Immunodeficiency Virus Treatment—Induced Adipose Tissue Pathology and Lipoatrophy: Prevalence and Metabolic Consequences

Emma Hammond, Elizabeth McKinnon and David Nolan

in Clinical Infectious Diseases

Published on behalf of Infectious Diseases Society of America

Volume 51, issue 5, pages 591-599
Published in print September 2010 | ISSN: 1058-4838
Published online September 2010 | e-ISSN: 1537-6591 | DOI: http://dx.doi.org/10.1086/655765
Human Immunodeficiency Virus Treatment—Induced Adipose Tissue Pathology and Lipoatrophy: Prevalence and Metabolic Consequences

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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.

Journal Article.  4865 words.  Illustrated.

Subjects: Infectious Diseases ; Immunology ; Public Health and Epidemiology ; Microbiology

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