Advances in HIV treatment and prevention have led to millions of perinatally HIV-infected (PHIV) and perinatally HIV-exposed, but uninfected (PHEU) children surviving into adolescence and young adulthood. Young adulthood can be a precarious developmental period, and PHIV young adults (YA) are at particularly high risk for mental health problems, risk behaviors, and difficulties achieving adult milestones due to a “perfect storm” of compromised health, life stressors, and neurocognitive deficits. These risks are exacerbated by inadequately controlled HIV, and psychosocial stressors encountered by both PHIV and PHEU YA, leading to chronic inflammatory responses that compromise psychiatric function, neurocognition, and overall health outcomes. For the past 15 years, CASAH has followed 340 PHIV and PHEU youth (enrolled at ages 9-16 years) living in vulnerable communities in New York City, documenting risk and resilience across childhood, adolescence, and emerging adulthood. This competing continuation of CASAH (R01-MH69133-15), CASAH4, will follow this cohort through young adulthood (20s-early 30s), leading to one of the most comprehensive longitudinal data sets on mental health, health risk behavior, and achievement of adult milestones among PHIV and PHEU YA. Guided by Social Action Theory (SAT), CASAH4 offers a unique opportunity leverage our unique longitudinal data set to understand the impact of both lifelong HIV infection and also contextual, social-regulation, and self-regulation determinants of mental health, health risk behaviors, and adult milestone achievement. In CASAH4 we aim to 1) examine the impact of HIV infection on behavioral health outcomes (e.g., mental health, sexual risk, substance use, adherence) and achievement of adult milestones (e.g., education, vocation, independence); 2) examine how SAT-informed risk and protective factors affect YA behavioral health and achievement of adult milestones; 3) explore trajectories of behavioral health across adolescence and young adulthood and SAT-informed predictors of these trajectories; and 4) compare behavioral health outcomes and their SAT-informed predictors among youth across three global cohorts by PHIV-status at early (9-12 years), middle (13-15 years), and late (16-19 years) adolescence. Building on our previous work, we will enhance our assessment of adult milestones, psychiatric function, and neurocognitive function, and will add biomedical health indicators (inflammation and immune activation biomarkers associated with psychiatric disorders and neurocognitive function) to the HIV RNA viral load and CD4+ cell count already collected. CASAH has made significant contributions to research on risk and resilience in PHIV and PHEU youth with 117 publications and 65 scientific presentations, and has directly informed mental- health and HIV-prevention interventions and service systems in the US and abroad. With a multidisciplinary and cross-cultural team, we have a unique opportunity to e...