PROJECT SUMMARY/ABSTRACT Background: Transgender women (TW) shoulder the highest prevalence of HIV compared to other key populations in the epidemic with 14% of all TW in the United States (US) living with HIV. HIV pre-exposure prophylaxis (PrEP) has been available in the US since 2012 yet uptake has been slow and challenges related to adherence have emerged. A comprehensive understanding of the socioeconomic, behavioral and systems factors that contribute to PrEP uptake, adherence and persistence among TW will illuminate potential mechanisms for optimizing PrEP engagement and reducing HIV incidence. Study Goal and Aims: This study will identify factors that will optimize PrEP uptake, adherence and persistence among transgender women at risk for HIV acquisition in the United States. Specific aims are to: 1) Identify groups of TW with distinct longitudinal PrEP engagement trajectories; 2) Examine associations between membership in each PrEP engagement group with demographic, socioeconomic, behavioral and systems indicators; and 3) Develop a model for the mechanisms by which socioeconomic, behavioral and systems factors impact TW's PrEP engagement trajectories. Approach: This explanatory, sequential mixed-methods study will leverage the data and infrastructure of an existing parent study, which has established a longitudinal cohort of 1,215 TW at risk of HIV acquisition in the United States. Aims 1 and 2 will be secondary analyses of longitudinal survey data collected by the parent study. Aim 1 will utilize group-based trajectory modeling, an extension of latent class analysis appropriate for longitudinal data, to identify groups of TW who follow similar patterns of PrEP uptake, adherence and persistence over 24-months of follow-up. Aim 2 will use multinomial logistic regression to identify factors associated with membership in each PrEP trajectory group identified in Aim 1. Building on findings from Aims 1 and 2, Aim 3 will qualitatively explore the mechanisms by which socioeconomic, behavioral and systems factors impact TW's PrEP engagement trajectories through in-depth interviews with TW and stakeholders. Findings will be triangulated to develop a more nuanced understanding of this important topic. Fellowship Information: The proposed research is the doctoral dissertation of Ms. Erin Cooney, PhD student at Johns Hopkins Bloomberg School of Public Health. The training is mentored by experts in HIV prevention including one Sponsor, two Co-sponsors, and two Scientific Advisors with complementary methodological and topical expertise. The training plan outlines formal coursework, ongoing mentorship, research implementation, and other advanced training opportunities to prepare Ms. Cooney to become a leading independent researcher in HIV prevention. The proposed study directly aligns with the NIMH's Division of AIDS Research priorities of expanding approaches to integrate behavioral science with effective biomedical strategies for HIV prevention.