PROJECT ABSTRACT This competing renewal to Suubi+Adherence study (R01HD074949) will examine the longitudinal HIV antiretroviral therapy (ART) adherence and related outcomes, and the potential mechanisms of protective health behaviors among youth living with HIV (YLHIV) who participated in an evidence-based family economic empowerment (FEE) intervention in Uganda and are now transitioning into young adulthood. Sub-Saharan Africa (SSA) has the highest HIV prevalence rate in the world. In Uganda, a poor SSA country hardest hit with HIV, the prevalence of viral load suppression among adolescents and young adults (15 to 24 years old) is 44.9% for females and 32.5% for males. For six years (2012-2018), the Suubi+Adherence study prospectively followed 702 YLHIV (aged 10 to 16 years at enrollment) randomized to two study arms across 39 clinics in Uganda: 1) control arm consisting of bolstered standard of care (BSOC) and 2) intervention arm consisting of BSOC and a FEE intervention. Study findings pointed to superior short-term viral suppression and positive child health and mental health functioning among the intervention arm. This renewal (Suubi+Adherence-Round 2) proposes to examine whether the results are maintained through young adulthood, an incredibly vulnerable transition period, particularly in areas of adherence to HIV treatment, cognitive development, mental health, sexual risk taking behaviors and alcohol/drug misuse. The renewal (2020-2025) will build on the Suubi+Adherence study to conduct one of the largest and longest running studies of YLHIV in SSA during a developmental period marked by profound biological and psychological maturation, and development transitional milestones. In this next phase, we will add a qualitative component to examine participants' experiences with the FEE program as well as long-term effects. Innovatively, we will also assess the impact of the FEE on cognitive functioning. The study specific aims are: Aim 1. To examine the long-term impact of the Suubi+Adherence intervention on: HIV viral suppression (primary outcome) and to explore the long-term impact of the intervention on key HIV treatment adherence outcomes for YLHIV, including participants' ability to access and refill prescribed medication, adhere to prescribed daily medication routines, and engage in HIV care; Aim 2. To elucidate the long-term effects of the Suubi+Adherence intervention on potential mechanisms of change, including: a) economic stability, sexual risk- taking behavior, adherence self-efficacy; b) cognitive functioning; c) mental health functioning; and d) young adult transitions and social support; Aim 3. To qualitatively examine– prospectively and retrospectively: a) multi- level factors affecting participants' maintenance of intervention benefits since Suubi+Adherence intervention initiation (prospectively); and b) participants' experiences with the intervention (retrospectively), including multi- level factors that may have influenced their engagement with the program and their decision-making in regard to ART adherence; Aim 4. To examine the long-term cost-effectiveness of the Suubi+Adherence intervention. The study is aligned with the National Institutes of Health Office of AIDS Research priorities.

PROJECT NARRATIVE As economically vulnerable youth living with HIV transition into young adulthood, they experience limited social support and compromised health, including inconsistent adherence to antiretroviral therapy and other health- related regimens, which elevates their vulnerability to virologic failure, poor mental health functioning, cognitive deficits, such as memory and executive functioning and other negative life outcomes, including risk-taking behaviors, leading to HIV transmission. The Suubi+Adherence-R2 study will extend the recently completed efficacious Suubi+Adherence study to examine the longitudinal outcomes related to adherence to HIV antiretroviral therapy (ART) as well as the potential mechanisms of protective health behaviors among youth living with HIV who have previously received an experimental family economic empowerment intervention and are now transitioning into young adulthood in Uganda. Aligned with the National Institutes of Health Office of AIDS Research priorities, the findings of this study may inform efforts to improve HIV care continuum among Uganda’s youth living with HIV, with potential replicability in other low-resource countries.