Serum for insulin determination was obtained at the same time, and all specimens were stored at 70C until the day of assay. higher than the HOMA without any cumulative stavudine use. Family history of diabetes, hepatitis C virus seropositivity, CD350 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. Keywords:antiretroviral therapy, HIV, HOMA, insulin resistance, nucleoside reverse transcriptase inhibitor, protease inhibitor == INTRODUCTION == Insulin resistance (IR) has been increasingly recognized in HIV-infected individuals since the introduction of effective antiretroviral therapy (ART). The protease inhibitor (PI) class of ART has most often been studied because early reports suggested an association between PIs and disorders of glucose metabolism.13Some recent studies have shown an association between the nucleoside reverse transcriptase inhibitor (NRTI) class, which is considered the mainstay of effective ART and IR.4,5 Few studies have investigated the interplay of HIV infection, ART use, and nonHIV-related factors with IR. An understanding of the relationship of these factors with IR is imperative, given recent evidence suggesting an increased risk of premature cardiovascular disease in HIV-infected individuals.69IR is an important risk factor for cardiovascular disease. To our knowledge, only 1 1 published prospective study investigated factors associated with IR within the context of HIV infection and relative to HIV-uninfected individuals, but that study was primarily limited to white men.4 We examine the association of both the type and duration of ART exposure and nonHIV-related factors with IR using IEM 1754 Dihydrobromide the homeostasis model assessment (HOMA) from October 2000 to March 2007 among participants from the Womens Interagency HIV Study (WIHS), a large ethnically diverse prospective cohort of HIV-infected and HIV-uninfected women. == METHODS == == Setting and Participants == The WIHS is a multicenter IEM 1754 Dihydrobromide prospective cohort study established in 1994 to investigate the progression of HIV in women with and at risk for HIV. A total of 3766 women (2791 HIV-infected and 975 HIV-uninfected) were enrolled in either 19941995 (n = 2623) or 20012002 (n = 1143) from 6 US cities (Bronx, Brooklyn, Chicago, Los IEM 1754 Dihydrobromide Angeles, San Francisco, and Washington, DC). Baseline sociodemographic characteristics and HIV risk factors were similar between HIV-infected and HIV-uninfected women.10,11An institutional review board approved study protocols and consent forms, and each study participant gave written informed consent. Every 6 months, participants complete a comprehensive physical examination, provide biologic specimens for CD4 cell count and HIV RNA viral load determination, and complete an interviewer-administered questionnaire, which collects information on demographics, disease characteristics, and specific ART use. Beginning in October 2000, fasting glucose (FG) and insulin levels were measured after participants had fasted for 8 hours (except for intake of prescribed ART). Of the 2870 women with a visit between October 2000 and March 2007, 2583 had at least 1 FG and insulin measurement at the same visit; the first visit with both FG and insulin data available will be referred to as IEM 1754 Dihydrobromide the index visit. Of the 2583 women with an index visit, 68 were excluded due to either a positive (n = 60) or missing (n = 8) report of pregnancy at the index visit. Of the remaining 2515 women, 284 were excluded due to prevalent diabetes mellitus (DM) (defined as a FG 126 mg/dL or self-reported DM or self-reported anti diabetic IEM 1754 Dihydrobromide medication use, all at or before the index visit). Thirteen women who were HIV-uninfected at WIHS study entry and seroconverted during follow-up were also excluded. Our final study population consisted of 2218 women (1614 HIV-infected and 604 HIV-uninfected) who contributed a total of 11,019 visits with FG and insulin data. The median number.