July 14, 2003
This oral presentation by Dr. Hadigan reported on a study using rosiglitazone in patients with HIV-associated lipodystrophy. Rosiglitazone is a drug used in the management of diabetes. However, the drug is known to affect certain fat metabolism enzymes resulting in increased glucose uptake into cells, decreased fat breakdown and increased fat accumulation. Dr. Hadigan reviewed some prior data which provided the evidence and justification for the current study.
The current study is a randomized, double blind, placebo-controlled study in which people were given either 4 mg a day of rosiglitazone or placebo for three months. At the end of three months all patients were given open label rosiglitazone at 8 mg a day for an additional three months. Fat distribution and content was measured by CT and DEXA scans, and BIA. Subjects had to be on a stable HIV medication regimen, have evidence of fat atrophy and have elevated insulin levels. They could not have diabetes or evidence of kidney problems. Twenty-seven patients were enrolled, with a mean age of 45 and twice as many men as women. These patients had had HIV infection for several years and had received HIV medications for, on average, about seven years.
The results demonstrated that on average the rosiglitazone group had a 15 percent increase in total body fat compared to placebo. However, when the individual areas of fat were compared (subcutaneous abdominal fat, visceral fat and leg fat), there was no significant difference compared to placebo. Additional blood tests showed an increase in adiponectin (a protein made by fat cells, indicating increased activity of fat cells), a decrease in free fatty acids, and an increase in total cholesterol.
Dr. Hadigan presented the open label data using a higher dose of rosiglitazone. When compared to baseline, total body fat increased by 6 percent and subcutaneous abdominal fat by 14 percent, but visceral fat had not increased. Adiponectin increased 3.7 times compared to baseline. Patients also rated their own severity of lipodystrophy and self-reported a marked improvement (overall gain in body fat). There was on average a 15 percent increase in cholesterol and a small but significant reduction in hemoglobin, which are known side effects of this class of medication.
This study is important because lipodystrophy (fat redistribution and loss) and lipoatrophy (fat loss) are big problems for patients, particularly those receiving long-term protease inhibitor therapy. Numerous drugs and other modalities have been tried to arrest or reverse the process. The data presented here seems to indicate that rosiglitazone may be effective in increasing body fat in those patients with fat wasting. Whether the increases in cholesterol or decreases in hemoglobin are important side effects of this new strategy remains to be determined in larger studies.
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