PROJECT SUMMARY/ABSTRACT – OVERALL The RUSTBELT Center for AIDS Research (CFAR) is a close partnership between Case Western Reserve University and the University of Pittsburgh. The MPIs for the RUSTBELT CFAR will be Dr. Jonathan Karn at CWRU, who has directed the CWRU/University Hospital CFAR since 2008, and Dr. Sharon Hillier at the University of Pittsburgh, who is a leader in HIV prevention research. By combining the two complementary programs in Cleveland and Pittsburgh, a larger range of services and activities are offered. The research strengths in Cleveland and Pittsburgh will exploit natural synergies and increase the impact of our NIH-funded research programs through the development of regional interdisciplinary teams. The RUSTBELT CFAR has 242 members (216 Full; 41 Associate; 26 International) and an NIH-funded research base of over $56 M. The Aims of the RUSTBELT CFAR are to (1) provide scientific and administrative leadership to position the RUSTBELT CFAR at the forefront of HIV research (Administrative Core A), (2) promote new faculty development (Developmental Core B), (3) support cutting-edge international research in Uganda (Uganda Core C), (4) support state-of-the-art clinical research through access to an unrivaled set of clinical cohorts, a broad array of tissue specimens, cutting- edge clinical assays, and community outreach (Clinical Sciences Core D), and (5) develop and expand translational and basic research infrastructure to support innovative multidisciplinary HIV research (Viral Pathogenesis & Persistence Core E; Systems Biology and Biostatistics Core F). The highly interactive Cores will not only provide access to state-of-the-art technologies, bioinformatics, and expertise, but also actively participate in the development of new approaches that will be shared between the two institutions. Two scientific strategic working groups led jointly by mid-career investigators from each institution will stimulate new research initiatives across the RUSTBELT CFAR focused on Sex & Gender and Ending the HIV Epidemic (EHE). The RUSTBELT CFAR will increase and focus its efforts on HIV prevention in Cuyahoga County, one of the 48 counties targeted as a priority in the Presidential plan to end the epidemic, building on the successful implementation of AIDS-free Pittsburgh in Allegheny County. Strong institutional support from each of the universities paired with strong community engagement provides the foundations for successful implementation of the research plan. In summary, through its scientific leadership, mentoring, pilot funding, scientific Cores, community outreach, and unique programs in Uganda, the RUSTBELT CFAR has effectively positioned its investigators at the leading edge of HIV/AIDS research.