The use of highly active antiretroviral therapy (HAART) has led to dramatic improvements in survival among people with HIV/AIDS (PHAs) in North America and Western Europe who can adhere to complex drug regimens. However, HAART often has side effects, perhaps the most notorious of which is the lipodystrophy syndrome. This syndrome includes the following features:
It is not clear which of these features of lipodystrophy are caused by specific components of HAART, such as protease inhibitors (PIs), nucleoside analogues (nukes) and non-nukes. Some researchers think that HIV infection may also play a role in the lipodystrophy syndrome. To investigate the effect of PIs on the lipodystrophy syndrome, researchers in California conducted a short study of indinavir (Crixivan) in HIV negative subjects. Based on their results, it is clear that even as little as four weeks of exposure to indinavir can increase the risk of people developing diabetes.
Researchers recruited 10 healthy, HIV negative males whose average age was 42 years. Subjects entered a hospital for five days where they received meals containing a fixed amount of fat, protein and starch/sugar to help maintain body weight and also reduce the effect of diet on changes to insulin, glucose and lipid levels in their blood at the start of the study. At the end of their hospital stay, subjects began to take indinavir 800 mg every 8 hours for four weeks.
Commonly reported side effects during the study were as follows:
Results from several tests done by the researchers on subjects made it clear that all subjects developed problems with the way their bodies dealt with sugar once they started taking indinavir. Specifically, indinavir affected the body's ability to move sugar from the blood into cells where it could be used for energy. Indinavir does this in part by making cells less sensitive to the effect of insulin. These changes increase the risk of indinavir-users developing diabetes ? one subject did in fact develop this condition.
Researchers noted that those subjects who had family members with diabetes were more likely to be affected by indinavir's negative impact on blood sugar and insulin.
Overall, four weeks' exposure to indinavir had little effect on levels of fatty substances in the blood ? cholesterol, triglycerides, low-density lipoprotein and high-density lipoprotein. As well, no subject developed changes in body shape. Longer exposure to indinavir may have different results.
This study is a good first step in trying to sort out the possible causes of the lipodystrophy syndrome. Further work needs to be done with other PIs as well as in other populations, such as women, both before and after menopause.
REFERENCE
Noor MA, Lo JC, Mulligan K, et al. Metabolic effects of indinavir in healthy HIV-seronegative men. AIDS 2001;15(7):11-18.
20010610
CATE11802
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.
AEGiS is made possible through unrestricted grants from Boehringer Ingelheim, Elton John AIDS Foundation, iMetrikus, Inc., the National Library of Medicine, and donations from users like you. Always watch for outdated information. This article first appeared in 2001. This material is designed to support, not replace, the relationship that exists between you and your doctor.
AEGiS presents published material, reprinted with permission and neither endorses nor opposes any material. All information contained on this website, including information relating to health conditions, products, and treatments, is for informational purposes only. It is often presented in summary or aggregate form. It is not meant to be a substitute for the advice provided by your own physician or other medical professionals. Always discuss treatment options with a doctor who specializes in treating HIV.
