Antiretroviral therapy exposure and insulin resistance in the women's interagency HIV study

Background: Evidence suggesting an increased risk of cardiovascular disease in HIV-infected individuals has heightened the need to understand the relation of HIV infection, antiretroviral therapy use, and non-HIV-related factors with insulin resistance (IR). Methods: Prospective study of 1614 HIV-infected and 604 HIV-uninfected participants from the Women's Interagency HIV Study between October 2000 and March 2007. Homeostasis model assessment (HOMA)-estimated IR at 11,019 semiannual visits. Results: HIV-infected women reporting highly active antiretroviral therapy (HAART) had higher median HOMA than HIV-uninfected women {1.20 [95% confidence interval (CI): 1.11 to 1.30] times higher for those reporting protease inhibitor-containing HAART; 1.10 (95% CI: 1.01 to 1.20) times higher for those reporting non-protease inhibitor-containing HAART}. Among HIV-infected, cumulative exposure to nucleoside reverse transcriptase inhibitors (NRTIs) of >3 years was associated with HOMA 1.13 (95% CI: 1.02 to 1.25) times higher than the HOMA without any cumulative NRTI exposure. Cumulative exposure to the NRTI stavudine of >1 year was associated with HOMA 1.15 (95% CI: 1.05 to 1.27) times higher than the HOMA without any cumulative stavudine use. Family history of diabetes, hepatitis C virus seropositivity, higher body mass index, or reporting menopause was associated with higher HOMA. Conclusions: Longer cumulative exposure to NRTI; in particular, stavudine is associated with greater IR in HIV-infected women.