In order to find ways to help HAART-users who are experiencing blood sugar/insulin problems, researchers across the globe are studying exactly how indinavir (Crixivan) and nelfinavir (Viracept) cause these problems. At this time we don't have detailed information on the impact of other protease inhibitors (PIs) and their effect on insulin.
One source of the insulin/sugar problem is that PIs affect the ability of transporter proteins to move sugar (glucose) from the blood into cells. This problem occurs in muscle and fat cells, which are major users of glucose. Laboratory research in France suggests that the drug rosiglitazone (Avandia) helps reverse indinavir's damage to the glucose transporting proteins. Its effectiveness and safety in HAART-users needs to be confirmed in long-term studies.
Researchers in Israel have confirmed the negative impact of nelfinavir on the effect of insulin. The drug Rezulin (no longer available in many countries), in laboratory experiments, was able to reduce the level of insulin resistance caused by nelfinavir. Although Rezulin is very similar to other drugs such as rosiglitazone and pioglitazone (Actos) - all three drugs are commonly called glitazones - it is not clear if these other two drugs can help nelfinavir-users until results from clinical trials are analysed.
Changes to diet and exercise are simple ways of trying to help the body cope with insulin resistance. Sometimes, however, such steps may not be enough, and drugs such as metformin (Glucophage) and the glitazones or older anti-diabetic drugs may be necessary. For results from short trials of metformin in PHAs, see TreatmentUpdate 111. There are also several complementary therapies that may be considered for helping to manage blood sugar. Details on some of these other therapies will appear in a future issue of TreatmentUpdate.
REFERENCES
1. Nolte LA, Yarasheski KE, Kawanaka K, et al. The HIV protease inhibitor indinavir decreases insulin-and contraction-stimulated glucose transport in skeletal muscle. Diabetes 2001;50:1397-1401.
2. Murata H, Hruz PW and Mueckler M. The mechanism of insulin resistance caused by HIV protease inhibitors. Journal of Biological Chemistry 2000;275(27):20251-20254.
3. Rudich A, Vanounou S, Riesenberg K, et al. The HIV protease inhibitor nelfinavir induces insulin resistance and increases basal lipolysis in 3T3-L1 adipocytes. Diabetes 2001;50:1425-1431.
4. Caron M, Auclair M, Vigouroux C, et al. The HIV protease inhibitor indinavir impairs sterol regulatory element-binding protein-1 intranuclear localization, inhibits preadipocyte differentiation, and induces insulin resistance. Diabetes 2001;50:1378-1388.
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Copyright © 2001 - TreatmentUpdate. Reproduced with permission. Reproduction of this article (other than one copy for personal reference) must be cleared through the Editor, The Canadian AIDS Treatment Information Exchange, 555 Richmond St. West, Suite 505, Box 1104, Toronto, ON, M5V 3B1 • Phone: 416-203-7122 • Toll Free: 1-800-263-1638 • Fax: 416-203-8284 http://www.catie.ca.
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