Fat Redistribution and Metabolic Change in HIV Infection

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DESCRIPTION (provided by applicant): There is increasing concern over an epidemic of cardiovascular disease (CVD) in patients with HIV infection (HIV+), due to changes in fat distribution and lipid and glucose metabolism that appeared with the introduction of HIV protease inhibitors (PI). However, there is controversy over the role of PI. Data from the study of Fat Redistribution And Metabolic Change in HIV Infection (FRAM) predict increased CVD, but PI drugs are not the major risk factor. We found that other ARV and HIV itself contribute to abnormalities in fat distribution and metabolism. Smoking and microalbuminuria in HIV+ also contribute to CVD risk. It is crucial to determine whether atherosclerosis is increased in HIV+ and, if so, to define the contributors. FRAM is uniquely suited to examine the contributors to atherosclerosis in that a large number of randomly selected HIV-infected men and women from geographic and ethnically diverse populations, and well matched controls from a subset of the CARDIA study were studied with the same rigorous protocol. We assessed regional fat volumes, traditional metabolic risk factors, blood pressure, family history and habits. We propose a follow up to measure carotid intimal medial thickness (IMT) by ultrasound to determine the prevalence of atherosclerosis and contributing factors. We will repeat body composition by MRI, blood pressure, bone density by DXA, and habit survey, plus laboratories for traditional metabolic (e.g., glucose and lipid) and novel inflammatory (e.g., CRP, cytokines) CVD risk factors. Glucose tolerance and fat clearance will be performed. All studies will be done in the subjects from the last FRAM exam, but we will also compare IMT, laboratory results, blood pressure and habits to the larger CARDIA and MESA cohorts. Using multivariate step-wise logistic regression analysis we will assess the association of atherosclerosis by IMT with HIV independent risk factors such as smoking that may be increased in HIV+ cohorts and HIV influenced risk factors (e.g., glucose and lipid metabolism, inflammation). We will assess the association of HIV, ARV and the changes in fat distribution with the CVD risk factors and with IMT. The results will provide essential information on the risk of atherosclerosis and its contributors to aid in patient care, policy and future research.