Modified Project Summary/Abstract Section In 2017, new HIV infections in Chicago decreased somewhat, and 92% of persons diagnosed with HIV were linked to care within 12 months of diagnosis. However, major problems remain. Only 36% of persons living with HIV (PLWH) in 2017 were retained in care, and only 48% achieved viral suppression. In addition, successes of antiretroviral therapy (ART) have led to a rising population of older PLWH, which has made aging-related comorbidities a proximate threat to well-suppressed PLWH and ultimately an increasing public health challenge. Thus, the needs to improve real-world effectiveness of treatments, as well as HIV prevention, continue. The Clinical Sciences Core (CSC) will intensify its support of research that addresses these problems, building on infrastructure and linkages that we have created within and between Northwestern University (NU) and the University of Chicago (UC). An expanding group of community organization partners also increases reach to service providers, now notably including Howard Brown Health (HBH) that has expanded sites to areas of most need in Chicago. Offering CSC expertise and services across disciplines and institutions is central to our mission and supports the development of new scientific partnerships. This expertise includes human subjects research on streamlining ART and studying aging-associated comorbidities and inflammation. Our accomplished and dynamic Clinical Informatics Group (CIG) will continue advancing researcher access to sophisticated techniques for computation, analyses of Electronic Health Record (EHR)-derived data, and emerging digital tools for research participants. The CSC also emphasizes disseminating research findings and best practices, as well as engaging with community-based clinics and HIV screening programs. The long-term goal of the CSC is to significantly increase the number of outstanding clinical investigators, and the interdisciplinary resources available to them, in order to fuel discoveries that will propel us towards the end of the HIV epidemic. The CSC’s specific aims to reach this goal are to: 1) support clinical research that interacts with HIV-infected and with risk participants, and/or obtains and studies clinical data and specimens from them; 2) catalyze and support new research on non-AIDS comorbidities, including clinical phenotyping and pathophysiology of inflammation and accelerated aging in HIV; 3) expand research collaborations and linkages among study participants, clinical HIV researchers, HIV care providers, other implementation partners and trainees. In the next project period, the CSC commits to expanding the scope and impact of research on non-AIDS comorbidities among PLWH on ART as a major contributor to TC CFAR’s Overall aim 2. Each of the CSC specific aims contributes to Overall aim 2 on non-AIDS comorbidities, and the intent is to increase the CSC users’ multi-disciplinary research on aging and comorbidities in HIV.