The Chicago component of the Multicenter AIDS Cohort Study (MACS) is composed of a representative sample of men infected with HIV or at risk for such infection. We are in the third decade of research with three clinical sites located at the Howard Brown Health Center, the Northwestern University HIV/AIDS Clinic and the CORE Center of Cook County Hospital. The collected data and specimens from the participants have provided and will continue to provide detailed information about the role of host and environmental factors in HIV disease. During the next funding cycle (2009 to 2014), we will support studies of the natural and treated history of HIV infection and HIV-associated disease in the era of highly active antiretroviral therapy (HAART) through standardized and detailed data and specimen collection at 6-month intervals to characterize exposures and risk factors. We will support ongoing MACS-wide research projects and initiate new projects on: behaviors enhancing transmission of HIV-1;the responses, effects, and predictors of response to HAART including the impact of illicit drug use;the effects of aging on the clinical course of HIV, HIV therapy, and response to HIV therapy;the host environment interaction between host genetics and HIV and other exposures;and the impact of aging, HAART and/or HIV infection on end-organ disease, cancer (both AIDS-related and non-related) upon long-term survival of infected men. We will contribute to each of the aims through scientific leadership, development and implementation of the overall MACS scientific agenda, retention and maintenance of the cohort and development of a state of the art facility using novel technology to conduct MACS-wide investigations of host genetics. RELEVANCE (See instructions): The study will address transmission of HIV, the impact of HAART, its adverse effects and the interaction of therapy and aging upon the long-term survival of individuals with chronic inflammation due to HIV infection. Results will provide direction to efforts designed to reduce behaviors that enhance transmission and insights into the management of HIV-infected persons. Immunologic, virologic and genetic evaluation of men resistant to acquisition of HIV infection or demonstrating long-term non- or slow progression will aid in the development of a vaccine.