PROJECT ABSTRACT Globally, adolescents and young adults (AYA; ages 14-29) represent 30% of HIV incidence cases among persons of reproductive age, with ~75% occurring in Sub Saharan Africa (SSA). HIV incidence rises rapidly in SSA, as AYA leave school (often prematurely) and migrate for work and marriage. Older adolescents are more likely to experiment with health compromising behaviors that increase their vulnerability to HIV and sexually transmitted infections (STIs). Young people orphaned by AIDS [YPoAIDS]), 80% of which live in SSA represent a particularly vulnerable and unique population. Most YPoAIDS in SSA experience immense hardships, including higher rates of HIV risk behavior and odds of HIV infection. These adversities cumulatively disrupt the developmental milestones for YPoAIDS and can compromise their health and emotional wellbeing. Notably, our team has had great success with implementing a 6-year, three-armed RCT that tested a family-based economic intervention, Bridges (R01HD070727), among 1,383 primary school going adolescents in rural Uganda (10-14 years of age at enrollment) who lost one or both parents to AIDS. With over 90% retention rate over a 6-year period (2012-2018), our findings show efficacy of this contextually-driven intervention significantly improving sexual health, school retention and performance, and mental health. Yet, two critical policy and programming questions related to HIV prevention and engagement in care continuum remain unaddressed: 1) longer-term effectiveness of Bridges across YPoAIDS’s life course is currently unknown but critically important because of unique vulnerabilities during the transition into young adulthood; and 2) self-reports of sexual health are unreliable, hence the need to integrate biomarkers to provide the most precise results of these highly relevant (but currently unknown) sexual health outcomes among our participants. Thus, the specific aims of the Bridges- Round 2 study are: Aim 1. Examine the long-term impact of Bridges on: HIV prevalence (measured via participant’s HIV status) (Primary outcome); and b) Explore in secondary analyses the long-term impact of Bridges on key developmental and behavioral outcomes (e.g., mental health, alcohol and drug misuse); Aim 2. Elucidate the long-term effects of Bridges on potential mechanisms of change, including: a) economic stability, viral suppression (for ALHIV); PrEP use (for HIV negative adolescents), medical male circumcision (for boys); and b) young adult transitions; Aim 3: Qualitatively investigate participants’ experiences with Bridges that may have influenced engagement with the program, sexual risk-taking decisions, financial behaviors; experiences with developmental transitions; and perceptions on program sustainability; Aim 4: To assess the long-term costs and benefits of Bridges using formal economic evaluation. Our long-term goal is to translate knowledge into sustainable, theoretically-guided prevention and treatment effort...