HIV PROTEASE INHIBITORS AND ATHEROSCLEROSIS

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PROPOSAL: (Adapted from the applicant's abstract): Dr. Stein will develop a career in patient-oriented research by obtaining advanced training in clinical research design, biostatistics, lipoprotein biochemistry, and advanced ultrasound research techniques. He also will receive training in the ethical conduct of human subjects research. His long-term goal is to become a nationally and internationally recognized clinical investigator who develops therapeutic strategies and tests for the diagnosis and management of patients with or at risk for atherosclerotic vascular disease. As part of his research career development plan, Dr. Stein will complete the UWMS Clinical Investigator Preparatory Pathway (CIPP). As part of this program, he will obtain advanced training in research design, biostatistics, and epidemiology through courses and directed study in the UWMS Biostatistics and Medical Informatics Statistical Data Analysis Center. He will obtain training in lipoprotein biochemistry and lipid laboratory techniques through courses and directed study in the UWMS Hospital Lipid and Lipoprotein Laboratory. He will obtain training in advanced carotid ultrasound research techniques in the Center for Medical Ultrasound at Wake Forest University (WFU). Additional instruction regarding ethics and human subjects research regulations, leadership, teaching, and scientific writing are components of the career development plan. The research plan will determine whether the metabolic changes associated with use of human immunodeficiency virus (HIV) protease inhibitors are atherogenic, as determined by their effects on endothelial function (measured by flow-mediated vasodilation of the brachial artery) and early atherosclerosis (measured by carotid intimal-medial thickening). Abnormalities of these parameters, which are obtained by vascular ultrasound techniques, predict adverse cardiovascular events. Dr. Stein also will assess the effects of HIV protease inhibitors on atherogenic lipoproteins using the advanced lipid laboratory skills he obtains in the career development plan. Finally, Dr. Stein will determine if these medications impair postprandial clearance of triglyceride-containing lipoproteins by assessing lipid and lipoprotein responses to an oral fat load.