Inflammatory and Immune Mechanisms of Atherosclerosis in HIV-Infected Women

DESCRIPTION (provided by applicant): This investigation will examine immune, inflammatory, coagulation, and lipid disturbances as potential mediators of increased atherosclerosis in HIV-infected women participating in the Women's Interagency HIV Study (WIHS). Subjects will include 750 HIV-infected and 250 HIV-uninfected women participating in the Follow-up Phase of the WIHS Carotid Artery Ultrasound Study. The set of specific aims include two primary aims: Aim 1 focuses on established inflammation and coagulation biomarkers as predictors of subclinical atherosclerosis. Aim 2 examines lipid changes which constitute classic vascular risk factors. Data analysis goals are: (1) To correlate changes in inflammatory and coagulation markers with HIV disease stage and treatments, including initiation of HAART and changes in viremic and CD4+ status; (2) To determine if immune, inflammatory, and coagulation mechanisms contribute to increased atherosclerosis in HIV-infected women; (3) To determine changes in classic vascular risk factors (e.g., lipids) over time due to changes in HAART and HIV disease stage, and how this impacts atherosclerosis. In addition, we propose three exploratory aims examining novel immune and inflammatory mediators that may be of importance to atherosclerosis in HIV-infected adults: 1. Translocation of gut microbes, as measured by 16s RNA; 2. T-cell senescence (CD4+CD28- and CD8+CD28- T-cells); 3. T regulatory cells. This investigation will examine immune, inflammatory, coagulation, and lipid disturbances as potential mediators of increased atherosclerosis in HIV-infected women participating in the Women's Interagency HIV Study (WIHS). We will (1) correlate changes in inflammatory and coagulation markers with HIV disease stage and treatments, including initiation of HAART and changes in viremic and CD4+ status; (2) determine if immune, inflammatory, and coagulation mechanisms contribute to increased atherosclerosis in HIV-infected women; and (3) determine changes in classic vascular risk factors (e.g., lipids) over time due to changes in HAART and HIV disease stage, and how this impacts atherosclerosis. (End of Abstract)