Mechanisms of Atherosclerosis and CVD in HIV+ Women

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DESCRIPTION (provided by applicant): As survival among HIV-infected persons has improved markedly in the era of highly-active antiretroviral therapy (HAART), clarifying the long-term effects of both HIV infection and its treatment is increasingly important. Extensive data suggest that HIV-infected patients have premature atherosclerosis and cardiovascular events. However, several major questions regarding the causal mechanisms and clinical relevance of these findings remain unanswered. Atherosclerosis may be due to HIV infection, use of antiretroviral medications, or both. The well-known metabolic effects of protease inhibitors (Pis) or other antiretroviral drugs may promote atherosclerosis, or there may also be direct vascular effects of these medications. HIV lipodystrophy syndrome, either due to medications or HIV itself, may also be a contributing factor. Little is known about the potential atherogenic effects of sustained elevations of inflammation markers in HIV infection. Moreover, women, African-Americans and Hispanics have been underrepresented in studies of atherosclerosis and CVD in HIV infection. The overall goal of this investigation is to assess whether HIV-infected women have accelerated atherosclerosis and to identify potential mediators of atherosclerosis in HIV infection. Within the Women's Interagency HIV Study (WIHS) cohort, this study will assess progression of subclinical atherosclerosis using B-mode ultrasound imaging methods to measure changes over time in carotid artery intima-media thickness (IMT). The study will include 250 women with HIV infection and 250 HIV-negative controls at the six WIHS clinic sites. Carotid ultrasounds will be obtained at annual intervals over 48 months, and rate of IMT progression will be interpreted centrally at the Core Imaging Facility. The extensive WIHS database, featuring data collected at study visits every six months, will be used to evaluate whether IMT progression may be associated with HIV infection; use of HAART, Pis, or other antiretrovirals; occurrence of AIDS, high HIV viral load, and low CD4 count; metabolic abnormalities including diabetes, lipodystrophy, and hypertriglyceridemia; and inflammation markers and endothelial adhesion molecules including high-sensitivity CRP, E-selectin, and ICAM-1. This investigation will have major implications for the development of strategies to predict, prevent, or reverse atherosclerosis in HIV- infected women.