Background: Lipoatrophy, subcutaneous fat wasting, is a stigmatizing complication of antiretroviral therapy (ART). Thiazolidenediones are potent PPARγ agonists and expected to reverse lipoatrophy.
Methods: We evaluated rosiglitazone’s effect on several facets of lipoatrophy: 1) limb fat, 2) surrogate markers cardiovascular disease, and 3) mechanistic measures. We conducted a 48-week randomized, double-blind placebo-controlled trial of rosiglitazone in HIV-infected subjects with lipoatrophy on thymidine nucleoside reverse transcriptase inhibitors (tNRTI)-sparing regimens.
Results: Rosiglitazone significantly (p=0.02) improved peripheral lipoatrophy in the absence of tNRTIs. Carotid intima media thickness (IMT), oxidative, and some inflammatory markers worsened over time in these subjects on stable ART, regardless of the rosiglitazone assignment.
Conclusion: In the absence of tNRTIs, rosiglitazone improved peripheral lipoatrophy. Observed limb fat improvement after rosiglitazone was not associated with changes in surrogate markers of cardiovascular disease or mitochondrial indices. Lipoatrophy can in part be overcome by the PPAR-γ pathway independent of mitochondrial toxicity.