Mechanisms of Atherosclerosis and CVD in HIV+ Women

As survival among HIV-infected persons has improved markedly in the era of highly-active antiretroviraltherapy (HAART), clarifying the long-term effects of both HIV infection and its treatment is increasinglyimportant. Extensive data suggest that HIV-infected patients have premature atherosclerosis andcardiovascular events. However, several major questions regarding the causal mechanisms and clinicalrelevance of these findings remain unanswered. Atherosclerosis may be due to HIV infection, use ofantiretroviral medications, or both. The well-known metabolic effects of protease inhibitors (Pis) or otherantiretroviral drugs may promote atherosclerosis, or there may also be direct vascular effects of thesemedications. HIV lipodystrophy syndrome, either due to medications or HIV itself, may also be a contributingfactor. Little is known about the potential atherogenic effects of sustained elevations of inflammationmarkers in HIV infection. Moreover, women, African-Americans and Hispanics have been underrepresentedin studies of atherosclerosis and CVD in HIV infection. The overall goal of this investigation is to assesswhether HIV-infected women have accelerated atherosclerosis and to identify potential mediators ofatherosclerosis in HIV infection. Within the Women's Interagency HIV Study (WIHS) cohort, this study willassess progression of subclinical atherosclerosis using B-mode ultrasound imaging methods to measurechanges over time in carotid artery intima-media thickness (IMT). The study will include 250 women withHIV infection and 250 HIV-negative controls at the six WIHS clinic sites. Carotid ultrasounds will be obtainedat annual intervals over 48 months, and rate of IMT progression will be interpreted centrally at the CoreImaging 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 abnormalitiesincluding diabetes, lipodystrophy, and hypertriglyceridemia; and inflammation markers and endothelialadhesion molecules including high-sensitivity CRP, E-selectin, and ICAM-1. This investigation will havemajor implications for the development of strategies to predict, prevent, or reverse atherosclerosis in HIV-infected women.