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Individuals involved in the criminal justice (CJ) system continue to be at disproportionate risk for HIV infection, and often have a greater prevalence of substance use and sexual related risk behaviors relative to their non-CJ involved peers. Pre-exposure prophylaxis (PrEP), a once daily antiretroviral medicine, is an evidence-based approach for reducing the risk of contracting HIV but limited data exist regarding the use of PrEP among CJ populations, especially in the U.S. South. This study was conducted at the Pulaski County Regional Detention Facility (PCRDF) in Little Rock, Arkansas (AR), the largest county jail in the state. We explored knowledge about PrEP and HIV, perceptions about PrEP feasibility in both the jail and community settings and barriers to PrEP program implementation, through in-depth qualitative interviews with 21 jail detainees. We purposively sampled individuals based on specific self-reported risk behavior, including sexual risk (both heterosexual and same-sex) and drug related risk (e.g. IDU), among all eligible individuals. We identified five primary themes from the interviews: 1) accessing healthcare during community reentry was a low priority; 2) perception of risk and interaction with people with HIV was low; 3) there are many barriers to disclosing HIV risk behaviors in jail settings; 4) knowledge of PrEP is low but willingness to use is high; and 5) multiple barriers exist to PrEP uptake post-release. Our findings are contextually unique and therefore have important implications for future implementation of PrEP access either within jail settings or linkage to PrEP post release. [ABSTRACT FROM AUTHOR]