Project Summary - Overview The newly developed CWRU (Case Western Reserve University) Center for Excellence on the Impact of Substance Use on HIV was conceived in August 2017 and was initiated to effectively promote excellence in basic, translational, and clinical research concerning the intersection between substance use and HIV. The Center for Excellence includes 12 NIDA-funded Investigators who collectively hold 9 R01, 2 DP1, 3 R34, 2 R44, 1 U01, and 2 K01 drawn from the CWRU School of Medicine, University Hospitals Cleveland Medical Center, MetroHealth Medical Center, the Cleveland Clinic Foundation, the Louis Stokes Cleveland Veterans Administration Medical Center, the CWRU Mandel School of Applied Social Sciences, the Begun Center for Violence Prevention Research and Education, and the Cuyahoga County, Lorain County, and City of Cleveland Departments of Health. Major research strengths in the Center for Excellence include impact of drug use on HIV immunopathogenesis, HIV latency and Cure, NeuroAIDS, gastrointestinal dysfunction, sexual risk behavior, and HIV and HCV co-infections. Our studies are anchored by advanced computational, systems biology, biomimetic models, and induced pluripotent stem cell (iPSC) technologies that provide the opportunity to perform meta-omics analyses of the impact of opioid, methamphetamine, cannabis, and cocaine misuse on several clinical, virological, immunological, behavioral, and neurological outcomes of HIV disease. The Center for Excellence has the following Specific Aims: • Provide scientific leadership to position the Center at the forefront of substance use disorder research and function as a national research resource for the study of drug use in persons with HIV. • Establish an administrative infrastructure that maintains fiscal and management oversight of the Cores. • Apply advanced Computational Biology, Primary Cells, Biomimetic models, and iPSC- derived Cells to study of the impact of substance use on HIV disease. • Support translational, clinical, and behavioral research through access to unique clinical cohorts of persons with substance use disorder with HIV and at risk for HIV. • Accelerate junior faculty development and encourage experienced faculty to enter the substance use research arena to support the next generation of investigators. • Participate in community outreach.

Project Narrative - Overview Substance misuse remains the second most common mode of exposure to HIV among AIDS cases nationwide, representing 31% of total diagnoses. In addition, substance use is associated with a more severe course of HIV disease, as shown by the poor immune reconstitution and an increased rate of co-morbidities. The Case Western Reserve University (CWRU) Center for Excellence creates a collaborative environment that strongly supports Substance Use in HIV research at CWRU and for our colleagues in other NIDA-sponsored Centers nationwide.