Effect of pioglitazone on HIV-1-related lipodystrophy: a randomized double-blind placebo-controlled trial (ANRS 113).

Background: Although thiazolidinediones have been shown to increase subcutaneous fat in congenital lipodystrophy, rosiglitazone did not show convincing results in HIV lipoatrophy. We assess a potential specific effect of pioglitazone in this setting.
Methods: One-hundred and thirty HIV-1-infected adults with self-reported lipoatrophy confirmed by physical examination were randomized to receive pioglitazone 30 mg once daily (n=64) or placebo (n=66) for 48 weeks. Changes in limb fat between weeks 0 and 48 were measured using dual-energy Xray absorptiometry. Subcutaneous and visceral fat was measured by single-slice computed tomography; fasting plasma measurements of glucose, insulin and lipids levels were recorded.
Results: Limb fat increased by 0.38 kg in the pioglitazone group and 0.05 kg in the placebo group at week 48 (mean difference 0.33 kg, 95% confidence interval [CI] 0.10-0.56; P=0.051) by intention-to-treat analysis. In patients not receiving stavudine, an increase of 0.45 kg versus 0.04 kg was observed (mean difference, 0.40 kg, 95% CI 0.12-0.69; P=0.013), but this was not seen in patients on stavudine (n=36; P=0.404). Overall, there was no significant difference in subcutaneous abdominal fat or in visceral fat areas on computed tomography at L4 vertebra. The lipid profile was not significantly different at week 48 except for levels of high-density lipoprotein cholesterol, which was improved in the pioglitazone group (+0.08 mmol/l versus -0.08; P=0.005).
Conclusions: Pioglitazone 30 mg once daily for 48 weeks improved limb fat atrophy in antiretroviral-treated HIV-1-infected patients, although clinical benefits were not perceived by the patients. Treatment did lead to a favourable lipid profile, however, suggesting that this thiazolidinedione should be considered in the context of HIV-related lipoatrophy.