PROJECT SUMMARY This K23 application outlines a novel area of clinical research that meets a growing public health need as people who inject drugs (PWID) represent a disproportionate number of new HIV cases with limited knowledge about the programming and linkage to care needed to support pre-exposure prophylaxis (PrEP) usage among this population. The research aims are designed to ensure Dr. Matthew Murphy's (PI) future research independence in HIV prevention and PrEP use for those with substance use disorders (SUD) at the greatest risk of HIV infection by providing preliminary data for a future R01 application. The specific aims of the K23 proposal are to 1) conduct qualitative interviews with 20 CJ-involved male PWID to evaluate barriers and facilitators to PrEP initiation, adherence, and linkage to care after release from incarceration; 2) develop a “PrEPare-for-Release” intervention and conduct an open label pilot intervention with 15 male PWID who are being released from incarceration and 3) conduct an RCT of the “PrEPare-for-Release” intervention among 100 male PWID who are being released from incarceration. In order to both achieve those aims and attain research independence, Dr. Murphy will receive training in HIV prevention approaches for those with SUD within the criminal justice (CJ) system, qualitative research methodology used to identify barriers and facilitators to HIV prevention care, approaches to behavioral intervention development and evaluation as well as training in the responsible conduct of research. The mentorship team, made up of leading experts in related fields of clinical and public health research from both Brown University and nearby Yale University, are incredibly well suited to ensure both successful attainment of the research aims as well as future research independence for the PI. Dr. Philip A Chan (primary mentor), as a leader in the field of PrEP clinical research, will be a key expert on the successful implementation of the PrEP care continuum for this population and conducting trials evaluating interventions to improve its use. Additional mentorship for this proposal includes Dr. Josiah Rich (co-mentor), a global leader on intervention development to improve SUD management and HIV infection risk during the period of transition from incarceration to the community, Dr. Amy Nunn (co- mentor), a leading expert on qualitative methodology related to PrEP care and health inequalities with significant prior experience working with CJ-involved populations, Dr. Trace Kershaw (co-mentor), a global leader on behavioral intervention development to reduce HIV infection risk in populations with SUDs, and Dr. Christopher Schmid (co-mentor), former chair of biostatistics at Brown's School of Public Health with significant experience in clinical trial design and an expert in quantitative methodology.