PROJECT ABSTRACT The estimated HIV prevalence among criminal justice (CJ) involved individuals is three times higher than the general population. Parolees on post-release supervision after release experience multi-level obstacles (e.g., lack of access to housing, employment) that act as barriers to HIV prevention efforts, making existing approaches to HIV prevention insufficient for reducing HIV incidence. Pre-exposure prophylaxis (PrEP) is a once daily medication (emtricitabine/tenofovir, FTC/TDF) that has demonstrated efficacy in preventing HIV among at-risk groups. Little is known about PrEP knowledge, acceptability, initiation, and sustained use among parolees recently released from prison or how these patterns vary by individual (HIV risk factor, sociodemographic characteristics), social (stigma, social support), and structural (housing, employment) factors. Therefore, we propose to conduct an observational, multi-site cohort study in North Carolina, Kentucky, and Florida—the Southern Pre-Exposure Prophylaxis [PrEP] Cohort Study among Parolees (SPECS-P). This study is guided by the Social Ecological Model and the NIMHD Minority Health and Health Disparities Research Framework, which both have a focus extending beyond the individual and acknowledge that multi-level (individual, social, and structural) factors play a role in the perpetuation of persistent health disparities. The specific aims of the proposed study are: 1) characterize PrEP knowledge and acceptability among parolees; 2) identify the multi-level factors that predict PrEP initiation and sustained use among parolees; 3) qualitatively assess the multi-level factors that affect PrEP acceptability, initiation and sustained use to inform future intervention development. The proposed project will be the first observational cohort study that includes a CJ involved population at extreme risk for HIV acquisition. Our study is aligned with the following high priority topics as defined by the NIH, NIMHD Science Visioning, and Office of AIDS Research: a) advancing evaluation of approaches to improve minority health or to reduce health disparities; and b) reducing incidence of HIV/AIDS and implementing strategies to improve entry into prevention services.