The applicant is a dentist committed to establishing a career investigating the connection between oral pathogens and systemic disease. His long-term goal is to characterize this connection, and to define its pathophysiology. The investigator hypothesizes that current treatment of HIV-1 infected persons with the use of highly active anti-retroviral therapy (HAART) will place these patients at higher risk for developing atherosclerosis, as mediated through metabolic complications of these agents. The candidate plans to develop and follow a longitudinal cohort of 100 HIV-1 infected patients for two years. He will examine the connection between periodontal pathogens and the development of endothelial dysfunction, a sub-clinical marker of atherosclerosis. Examining this relationship in a cohort of HIV-1 infected persons may allow for significant relationships to be detected more rapidly if, as suspected, HIV-1 infection and/or its treatment accelerates the development of atherosclerotic disease. He proposes that the relationship between oral pathogens and vascular disease within a HIV-1 population on HAART will be significantly correlated. This is the first study to examine this topic using this population of unique subjects and using measurements this sensitive and specific. The proposed research development plan will train the applicant to obtain a more in depth understanding of quantitative epidemiology, oral microbiology, atherosclerosis, and HIV/AIDS. A collaborative team of mentors and consultants has been assembled mostly within the immediate campus of Case Western Reserve University (CWRU). Primary sponsors are established NIH investigators, and each co-sponsor has expertise in their related facet of the study. Given the multidisciplinary nature of his project, this training environment is ideally suited to help the candidate meet his project and career goals. This career development plan will establish the applicant as an independent investigator poised to achieve his long-term goals. In light of the high prevalence of periodontal disease and cardiovascular disease (CAD) within the United States, this study, which proposes to clarify the relationship between oral microbiology and vascular pathology, could have profound implications on containing risk factors for CAD.