PROJECT ABSTRACT In response to PA-20-144 calling for innovations in HIV prevention, testing, adherence and retention to optimize HIV prevention and care continuum outcomes, we examine the impact and cost-effectiveness of an innovative multilevel intervention combining Multiple Family Groups (MFGs) for HIV stigma reduction (MFG-HIVSR) with a family economic empowerment (FEE) intervention versus a group-based HIV stigma reduction for Educators (GED-HIVSR) combined with MFG-HIVSR plus FEE (hereafter M-Suubi) on HIV treatment adherence and engagement in care among school-going adolescents living with HIV (ALHIV) in Uganda. HIV stigma remains a formidable barrier to HIV treatment adherence among adolescents in Uganda, contributing to low rates of medication adherence and viral suppression (less than 50%) and high attrition from HIV treatment services. ALHIV experience HIV stigma (internalized, anticipated and enacted) in various settings, including families and schools, the most important developmental contexts that should otherwise be supportive of their development and wellbeing. One of the unique features about education in Uganda and other countries in Sub-Saharan Africa is the high proportion (over 60%) of school-going adolescents enrolled in boarding secondary schools – which represent a form of parental opt-in institutionalized care. ALHIV in schools are more disadvantaged and have lower levels of HIV treatment adherence due to high levels of HIV stigma within schools, rigid school structures and routines, lack of adherence support and food insecurity. Within families, HIV stigma is perpetuated in various forms including discrimination and violence, often due to unfounded fears of infection—hence undermining the quality of family relations and supports for ALHIV. Building on our research and current evidence on HIV stigma reduction, we propose a multi-level three-arm cluster randomized study (M-Suubi) with the following specific aims: Aim 1: Examine the impact of M-Suubi on HIV viral suppression (primary outcome); and adherence to HIV treatment (keeping appointments, pharmacy refills, pill counts), and retention in care (secondary outcome); Aim 2: Examine the effect of M-Suubi on HIV stigma (internalized, anticipated and enacted), with secondary analyses to explore hypothesized mechanisms of change (e.g. depression) and intervention mediation; Aim 3: Assess the cost and cost-effectiveness of each intervention condition; and Aim 4: Qualitatively examine: a) participants’ experiences with HIV stigma, HIV treatment adherence, and the intervention; and 2) educators’ attitudes towards ALHIV, experiences with GED-HIVSR, and program/policy implementation post-training. The study will enroll 840 ALHIV recruited from 42 schools located within the greater Masaka region, heavily affected by HIV (prevalence 12% vs 7.3% national average). M-Suubi will be provided for 20 months, with assessments at baseline, 12, 24 and 36 months. Findings may inform combin...