Modified Project Summary/Abstract Section 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 are Dr. Jonathan Karn at CWRU, who has led the CWRU/University Hospital CFAR since 2008, and Dr. Sharon Hillier at the University of Pittsburgh, a leader in HIV prevention research. By combining the two complementary programs in Cleveland and Pittsburgh, a broader range of services and activities is offered. The research strengths in Cleveland and Pittsburgh will leverage complementary skills to increase the impact of our NIH-funded research 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 exceeding $45 million. The CFAR aims to: (1) provide scientific and administrative leadership to position it at the forefront of HIV research (Administrative Core A); (2) support new faculty development (Developmental Core B); (3) pursue innovative studies in the US with samples from HIV+ individuals in Uganda (Uganda Core C); (4) support advanced clinical research with access to extensive clinical cohorts, numerous tissue samples, cutting-edge clinical assays, and community outreach (Clinical Sciences Core D); and (5) develop and expand research infrastructure for innovative interdisciplinary HIV research (Viral Pathogenesis & Persistence Core E; Systems Biology and Biostatistics Core F). These highly interactive cores will provide access to advanced technologies, bioinformatics, and expertise, while actively developing new approaches shared between the two institutions. Two scientific strategic working groups, led jointly by mid-career investigators from each institution, will promote new research initiatives focused on HIV Across the Lifespan (HAL) and Ending the HIV Epidemic (EHE). The CFAR will focus more on HIV prevention in Cuyahoga County, one of 48 counties prioritized in the Presidential plan to end the epidemic, building on the success of AIDS-free Pittsburgh in Allegheny County. Strong institutional support from each university, along with active community engagement, provides a solid foundation for successfully implementing the research plan. In summary, through its scientific leadership, mentoring, pilot funding, core facilities, community outreach, and access to unique clinical specimens from Uganda, the RUSTBELT CFAR has positioned its investigators at the forefront of HIV/AIDS research.