Transgender-specific Differentiated HIV Care Models: An Implementation Science Study Project Summary/Abstract Despite a disproportionate burden of HIV, transgender people are less likely to achieve viral suppression than the general population and have low engagement in PrEP services. Intervenable barriers to their engagement in HIV services include facility-based stigma and lack of access to gender affirming care, including hormone therapy. Transgender-specific differentiated service delivery models have recently been implemented as demonstration projects in South Africa, providing a unique opportunity to assess feasible and acceptable implementation strategies as well as analyze the effectiveness and cost of integrating gender affirming hormone therapy and stigma-reduction strategies into HIV care for transgender people. This observational, multi-site, mixed methods prospective implementation study will be guided by the Gender Affirmation Framework and the RE-AIM (Reach, Effectiveness, Adoption, Implementation, Maintenance) implementation science evaluation framework to meet the following aims: (1) assess barriers, facilitators, acceptability, and feasibility of transgender-specific differentiated service delivery using site observation checklists, key informant interviews with facility staff, and longitudinal in-depth interviews with transgender clients; (2) evaluate the effect of transgender-specific differentiated service delivery on viral suppression and PrEP adherence - testing stigma and gender affirmation as mediators, using a longitudinal cohort of TGP clients that compares transgender people enrolled at transgender-specific differentiated service delivery sites with transgender people enrolled in standard service delivery sites (200/arm on ART and 100/arm on PrEP for a total N = 600); and (3) estimate the cost associated with transgender-specific differentiated service delivery versus standard service delivery sites using a micro-costing approach to estimate the cost per service user served and per service user successfully treated at transgender-specific differentiated service delivery sites relative to standard service delivery sites, as well as the budget needed for successful South Africa-wide implementation.