PI Perspective #48

March 2009     View PDF     En español

Limb fat wasting improves with rosiglitazone therapy

The drug for treating diabetes, rosiglitazone (ROSI) improved lipoatrophy and insulin levels in people not taking thymidine NRTIs, which include Retrovir (AZT, zidovudine) or Zerit (d4T, stavudine). ROSI works by increasing the activity of a specific cell protein (called PPAR-gamma) that helps to break down fats in the body. Thymidine NRTIs significantly inhibit PPAR, and thus can cause changes in fat distribution, such as fat loss, called lipoatrophy.

This double-blind study followed 71 people with lipoatrophy. All stopped their NRTIs at least 24 weeks before study entry, although the average length was 4 years. They were randomized to take either 4mg ROSI twice a day or placebo for 48 weeks. DEXA scans (to measure fat content and bone density) and fasting metabolic tests (to measure insulin levels) were done throughout the study. Facial fat loss was not evaluated in this study.

Women made up 17% of the study participants, average age was 50 years, and 51% were white. About 92% of people had viral loads below 400, and characteristics at study entry were similar between the groups. Average limb fat was ~6500g for ROSI group and ~6400 for placebo. Volunteers could display some amount of insulin resistance, but those with diabetes were excluded from the study.

The results showed that the ROSI group had more significant increases in limb fat on average by 911g vs. 253g on placebo. The percentage of gained limb fat was also higher in ROSI group at 15% vs. 5% on placebo. Triglycerides and cholesterol levels did not change significantly within or between the groups. As well, lipid levels and bone density were not affected by ROSI therapy. According to the researchers, ROSI significantly improves lipoatrophy in people not on a thymidine NRTI. Though ROSI may be a promising therapy for improving lipoatrophy, people on thymidine NRTIs may do best by changing to a regimen without these NRTIs before adding ROSI therapy to their HIV health care.