PROJECT SUMMARY Incarcerated people are one of the key populations at the center of the HIV epidemic in Zambia and sub-Saharan Africa (SSA) in general. The periods during and after incarceration likely represent times of significant HIV risk, yet little is known about HIV infection vulnerability during these times or how best to provide incarcerated people with HIV prevention services such as pre-exposure prophylaxis (PrEP) to reduce HIV risk. To address these knowledge gaps, we propose the Prison PrEP Values, Adherence, and Implementation in Lusaka (PreVAIL) study. Our scientific premise is that providing effective combination prevention to incarcerated and justice- involved populations requires understanding both temporal changes in their HIV risk and patterns of their PrEP uptake, adherence, and persistence. The long-term goal of this work is to optimize the timing and delivery of PrEP, as part of combination prevention, for justice-involved persons in Zambia. The objective of this R21 is to characterize PrEP uptake, adherence, and persistence, as well as HIV risk perceptions and behaviors, among justice-involved persons during incarceration and transition to the community. PreVAIL builds on a robust platform for corrections-health research and service delivery in Zambia. The TasP study (Co-PI: Herce) was the first to assess universal test and treat for HIV for incarcerated people in SSA, the NIH-funded CONTINUUM study (PI: Herce) was one of the first studies to follow incarcerated people after release in SSA, and the CDC/PEPFAR-funded CIRKUITS project (PI: Claassen, Co-PI: Herce) is conducting one of the first demonstrations of PrEP for justice-involved people in SSA. In Aim 1 we will assess PrEP uptake, adherence, and persistence, as well as HIV risk factors and perception of HIV risk, among justice-involved people during incarceration and post-release. We will prospectively enroll a cohort of 800 HIV-negative and PrEP-eligible incarcerated people at prison entry and offer them oral PrEP. We will follow all cohort members for 12 months regardless of PrEP status, both during incarceration and following release. Primary outcomes include PrEP uptake, adherence, and persistence, as well as HIV status, HIV risk behaviors and risk perception. PrEP adherence will be assessed through self-report and a novel point-of-care urine tenofovir test. In Aim 2, we will use qualitative research methods to explore and understand barriers and facilitators of PrEP uptake, adherence, and persistence during incarceration and after release. We will purposively sample 40 participants from our cohort for theory-informed longitudinal in-depth interviews to understand multi- level barriers and facilitators to efficacious PrEP use, as well as PrEP method and service delivery preferences. This study will provide new insights into HIV risk for justice-involved people in Africa and quantify the magnitude of the gap in HIV prevention service continuity, leading to a future,...