Important note: Information in this article was accurate in August 2000. The state of the art may have changed since the publication date.
Given the results from the experiments on indinavir reported above, it's not surprising that people taking HAART regimens develop high levels of insulin and sugar in their blood. In addition to high levels of fatty substances in their blood, some PHAs also have elevated levels of a protein called tPA that helps blood to clot. All of these factors increase the risk of developing cardiovascular disease.
To help bring insulin and sugar levels back to normal, doctors may treat their patients with several drugs, one of which is metformin (Glucophage). An advantage that metformin has over other anti-diabetic drugs is that it can also help people lose weight. Doctors in France and the United States have studied metformin use in PHAs with lipodystrophy syndrome. More recently, American researchers have begun analysing the effect of metformin on tPA levels.
Researchers presented data on 25 HIV-positive subjects enrolled in a placebo-controlled study of metformin. Subjects took 500 mg of metformin twice daily for three months. The researchers found that subjects with lipodystrophy had tPA levels that were twice as high as normal. Subjects given metformin had statistically significant decreases in tPA, insulin, sugar and blood pressure compared to those subjects who did not receive metformin. Given that such changes are associated with a reduced risk of cardiovascular disease in metformin users without HIV, the same effect is likely to occur in HIV-positive people who use the drug.
Although the results of this placebo-controlled study are very promising, it's important to keep in mind that the study lasted only three months. Also, it should be noted that metformin has been associated with the development of lactic acidosis in some people. Moreover, blood clots are not the only factor that increases the risk of cardiovascular disease. Indeed, researchers in Wisconsin have found that the blood vessels of people taking protease inhibitors become less flexible, and researchers in Italy have observed that blood vessels become narrower. German researchers have confirmed some of these findings. Clearly, the results of the long-term study of metformin use in people treated with HAART will be of great interest.
1. Hadigan C, Meigs JB, Rabe J, et al. Increased tPA antigen levels in the HIV lipodystrophy syndrome are reduced in response to metformin. Abstract 022.
2. Egger M. Metabolic complications of HAART: need for perspective. Abstract 023.
3. Hadigan C, Corcoran C, Basgoz N, et al. Metformin in the treatment of HIV lipodystrophy syndrome: a randomized controlled trial. Journal of the American Medical Association 2000;284:472-477.
4. Sosman J, Klein M, Belleheumeur J, et al. Use of protease inhibitors is associated with endothelial dysfunction. Abstract 24.
5. Pan A, Seminari E, Voltini G, et al. Intima media thickness as cardiovascular risk marker in HIV-positive patients treated and untreated with protease inhibitors. Abstract 025.
6. Weber T-J, Bengel F, Bogner J-R, et al. Cardiovascular dysregulation in HIV-infected individuals treated with HAART. Abstract 026.
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