For their study of the glitazone Actos (pioglitazone), researchers in Geneva recruited nine HIV positive subjects who were using HAART. That all subjects were taking anti-HIV drugs is important because Actos is processed in the liver by the same enzyme that helps break down protease inhibitors and non-nukes. This enzyme is called p450 3A4. Researchers gave Actos at a dose of 30 to 45 mg/day for six months.
On average, subjects did not experience significant changes in weight. Levels of cholesterol remained stable while triglyceride levels showed a trend to decrease over time. Insulin resistance was normal at the start of the study and remained that way throughout the trial. X-ray scans did not detect any significant changes in fat redistribution over a period of six months.
Importantly, Actos did not appear to cause any dectable liver damage. Viral load levels remained stable in eight of nine subjects over the six months of the study.
Although controlled studies of Actos in HIV positive people are needed, the results of this small, short-term study suggest that Actos does not interfere with anti-HIV medication levels in the blood. Actos may also stop lipodystrophy from becoming worse, as four of nine subjects claimed that their fat redistribution improved while taking Actos.
Future studies of Actos in HIV positive people need to focus on the long-term impact of this drug on the following areas:
REFERENCES
1. Maeda K. Hepatocellular injury in a patient receiving pioglitazone. Annals of Internal Medicine 2001;135(4):306.
2. Haskins JR, Rowse P, Rahbari R, de la Iglesia FA. Thiazolidinedione toxicity to isolated hepatocytes revealed by coherent multiprobe fluorescence microscopy and correlated with multiparameter flow cytometry of peripheral leukocytes. Archives of Toxicology 2001;75(7):425-38.
3. Gosset P, Charbonnier AS, Delerive P, et al. Peroxisome proliferator-activated receptor gamma activators affect the maturation of human monocyte-derived dendritic cells. European Journal of Immunology 2001;31(10):2857-65.
4. Calmy A, Hirschel B, Karsegaard L, et al. A pilot study for the use of pioglitazone in the treatment of highly active antiretoviral therapy lipodystrophy syndromes. Abstract 43 - 3rd International Workshop on Adverse Drug Reactions and Lipodystrophy in HIV, 23-26 October 2001, Athens, Greece.
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