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Longer Exposure to NRTIs, especially Stavudine, Increases the Risk of Insulin Resistance in Women with HIV

As people with HIV live longer thanks to effective antiretroviral therapy (ART), cardiovascular disease and long-term metabolic problems are a growing concern, leading researchers to focus on the relationship between these conditions, HIV infection itself, and antiretroviral treatment. As reported in the December 1, 2008 Journal of Acquired Immune Deficiency Syndromes, Phyllis Tien and colleagues looked at factors associated with insulin resistance, which may progress to diabetes and can increase the risk of cardiovascular disease.

This prospective study included 1614 HIV positive and 604 HIV negative at-risk participants in the Women's Interagency HIV Study (WIHS) followed between October 2000 and March 2007. Insulin resistance, estimated using the homeostasis model assessment (HOMA-IR) method, was evaluated during a total of 11,019 semiannual visits.

Results

  • HIV positive women reporting HAART use had a higher median HOMA-IR score than HIV negative women:
  • 1.20 times higher for those using protease inhibitors (PIs);
  • 1.10 times higher for those using PI-sparing HAART.
  • Among the HIV positive women, cumulative exposure to nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) for > 3 years was associated with a median HOMA-IR score 1.13 times higher that of women with no NRTI exposure.
  • Cumulative exposure to the NRTI stavudine (d4T; Zerit) for > 1 year was associated with a HOMA-IR score 1.15 times higher than that of women who never used this drug.
  • Other factors associated with a higher HOMA-IR score were family history of diabetes, hepatitis C virus (HCV) seropositivity, higher body mass index, and menopause.

Based on these findings, the study authors concluded, "Longer cumulative exposure to NRTI[s], in particular stavudine, is associated with greater insulin resistance in HIV-infected women."

Stavudine has been linked to a variety of metabolic and other side effects, and is no longer considered a preferred NRTI according to U.S. and European treatment guidelines.

Department of Medicine, University of California, San Francisco, and San Francisco Veterans Affairs Medical Center, San Francisco, CA; Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD; Department of Medicine, University of Southern California, Los Angeles, CA; CORE Center-Stroger Hospital of Cook County, Chicago, IL; Department of Medicine, State University of New York Downstate Medical Center, Brooklyn, NY; Department of Medicine, Georgetown University Medical Center, Washington, DC; Departments of Epidemiology and Medicine, Columbia University, New York, NY.

1/30/09

Reference

PC Tien, MF Schneider, SR Cole, and others. Antiretroviral Therapy Exposure and Insulin Resistance in the Women's Interagency HIV Study. Journal of Acquired Immune Deficiency Syndromes 49(4): 369-376. December 1, 2008. (Abstract).