Context: The expression of adipogenic genes in subcutaneous adipose tissue has been reported to be lower among patients with human immunodeficiency virus (HIV)-associated lipoatrophy than HIV-uninfected controls. It is unclear whether this is a result or cause of lipoatrophy.

Objective: To investigate the temporal relationships among changes in adipogenic gene expression in subcutaneous adipose tissue and changes in body fat distribution and metabolic complications in HIV-infected subjects on antiretroviral therapy.

Design: Prospective longitudinal study.

Setting: HIV clinics in Seattle, WA.

Participants: 31 HIV-infected and 12 control subjects.

Interventions: Subjects were followed for 12 months after they initiated or modified their existing antiretroviral regimen.

Main outcome measures: Changes in body composition, plasma lipids, insulin sensitivity, and gene expression in subcutaneous abdominal and thigh adipose tissue.

Results: Subjects who developed lipoatrophy (n=10) had elevated fasting triglycerides [3.16 (SD 2.79) mmol/L] and reduced insulin sensitivity as measured by frequently sampled intravenous glucose tolerance test [1.89 (SD 1.27) x 10^-4 min^-1 per µU/mL] after 12 months, while those without lipoatrophy (n=21) did not show any metabolic complications [triglycerides 1.32 (SD 0.58) mmol/L, p=0.01 vs. lipoatrophy; insulin sensitivity 3.52 (SD 1.91) x 10^-4 min^-1 per µU/mL, p=0.01 vs. lipoatrophy]. In subjects developing lipoatrophy, the expression of genes involved in adipocyte differentiation, lipid uptake, and local cortisol production in thigh adipose tissue was significantly reduced already at the 2 month visit, several months before any loss of extremity fat mass was evident.

Conclusions: In HIV-infected subjects, lipoatrophy is associated with elevated fasting triglycerides and insulin resistance, and might be caused by a direct or indirect effect of antiretroviral drugs on subcutaneous adipocyte differentiation.