The overall scientific goal of this proposal is to determine how host genetic factors relate to adverse effects commonly observed in HIV infection. To achieve this goal, we will analyze DNA samples extracted from participants of a previously established cohort of 327 HIV-infected patients from a large longitudinal study that examines nutritional status in HIV infection. Polymorphisms in the genes commonly linked to metabolic and morphologic abnormalities in the general population will be determined in HIV-positive individuals. Specifically, this proposal aims at examining the association of seven selected candidate genes with incidence and rate of progression of carotid intima-media thickness and coronary calcium scores, and with the presence of metabolic syndrome, all surrogate markers of future cardiovascular events. Finally, dietary intake and individual antiretroviral medications will be assessed for their interaction with candidate genes. We hypothesize that genetic mechanisms confer susceptibility to the development of metabolic and morphologic complications in HIV-infected individuals treated with selective antiretroviral regimens, since these complications do not occur in all exposed patients. This proposal is designed to provide an opportunity for the Principal Investigator (PI) to gain knowledge and skills in designing and conducting clinical and epidemiologic research under the supervision of an advisory committee comprised of highly qualified mentors in an environment ideally suited for the study of HIV disease and genetic analysis. Through coursework, seminars and supervised research, the PI will gain knowledge and expertise in techniques pertinent to the proposed research. This K23 award in combination with the PI's background in infectious diseases, nutrition, clinical epidemiology and biostatistics, will provides excellent potential for the development of a successful independent research career focused on patient-oriented research in the genetic epidemiology of complications in HIV infection. At the end of the award, the PI will be a competitive applicant for R01 funding. PUBLIC HEALTH IMPLICATIONS: The proposed study has significant clinical and public health implications as the results may affect the choice of future antiretroviral medications, dietary interventions, risk stratification guidelines and preventive strategies to avoid the metabolic and morphologic complications observed with HIV disease and its treatment, and may lead to directed interventions in the care of patients.