Mechanisms of Atherosclerosis and CVD in HIV+ Women

Project: Research project

Project Details

Description

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.
StatusFinished
Effective start/end date3/1/062/29/12

Funding

  • National Heart, Lung, and Blood Institute: $579,110.00
  • National Heart, Lung, and Blood Institute: $633,315.00
  • National Heart, Lung, and Blood Institute: $668,811.00
  • National Heart, Lung, and Blood Institute: $574,885.00

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