PROJECT SUMMARY/ABSTRACT Transgender women (TGW) are at high risk for HIV infection, and are an important, under-researched key population in sub-Saharan Africa. Globally, HIV acquisition risk among TGW is 14 times higher than other adults aged 15-49 years. Intersectional stigma and discrimination (ISD) experienced by TGW at the intersections of HIV, sexual orientation, gender minority identity and sex work results in poor engagement in care and suboptimal adherence to HIV pre-exposure prophylaxis (PrEP) and antiretroviral therapy (ART). Much work remains in addressing HIV-related ISD and scaling up treatment and prevention coverage for TGW. Two evidence-based ISD-reduction interventions are available -- (1) Health Policy Plus (HP+) Total Facility Approach (TFA) to Stigma Reduction (a clinic-level intervention) and (2) HIV Education, Empathy and Empowerment (HIVE3) (an individual- level intervention) -- but these have not been adapted and implemented for TGW in sub-Saharan Africa. HP+ and HIVE3 are complementary interventions that could be combined to reduce health facility- and individual-level stigma. However, research is needed to show if the adapted multi-level HP+/HIVE3 intervention, Ssimusango (means “no self-blame or blaming others” in Luganda), decreases HIV-related stigma and improves HIV outcomes for TGW. To address these questions, we will conduct a randomized wait-list controlled trial to test the preliminary effectiveness of Ssimusango on PrEP adherence and viral suppression, compared with standard of care, using a status-neutral approach i.e., engagement in care regardless of HIV status. We will also use qualitative methods to assess mechanisms and synergies of intervention delivery. Leveraging the multi- disciplinary expertise of our multi-national research team, and working at four health facilities in Kampala ranked lowest on the PEPFAR Uganda stigma scorecard, we propose the following specific aims: (1) adapt the HP+ and HIVE3 stigma-reduction interventions to address ISD for TGW in Uganda (intervention adaptation); (2) conduct a hybrid type 1 effectiveness-implementation trial with 120 TGW to pilot test the preliminary effectiveness of Ssimusango on (a) PrEP adherence and (b) viral suppression (intervention implementation); and (3) evaluate Ssimusango using qualitative methods and the Intersectionality-Enhanced Consolidated Framework for Implementation Research (intervention evaluation). Clinic-level implementation outcomes are adoption, fidelity, and sustainability assessed using key informant interviews, training attendance sheets, observation checklists, and rapid feedback surveys. Individual-level outcomes: (1) PrEP adherence at 3 and 6 months post-intervention, measured by urine tenofovir levels (primary outcome) and (2) viral suppression (HIV RNA <50 copies/mL) and (3) ISD reduction 6 months post-intervention (secondary outcomes). This multi-level approach to implementing ISD interventions will improve PrEP and ART adherence outcomes among TGW - “the most vulnerable of the vulnerable” -, build stigma research capacity in Uganda, and generate actionable data for scale-up and program implementation in Uganda and sub-Saharan Africa.

PROJECT NARRATIVE African transgender women (TGW) are a stigmatized and marginalized population with high HIV incidence, poor engagement in HIV care and suboptimal ART and PrEP use. Multi-level interventions to reduce intersectional stigma and discrimination could improve HIV outcomes for TGW by addressing immediately modifiable stigma drivers, centering TGW at the core of the stigma response, engaging opinion leaders and building partnerships with TGW. Stigma reduction and status-neutral approaches to HIV care have the potential to decrease HIV burden in this population - “the most vulnerable of the vulnerable” - and generate actionable data for scale-up and program implementation.