LGBTQ+ students in U.S. colleges experience disproportionately high rates of mental health disorders and HIV vulnerability—risks exacerbated in rural and Appalachian regions by structural stigma, provider shortages, and limited-service access. Despite this convergence, few interventions integrate mental health and HIV prevention in campus settings.

This systematic review (2015–2024) analyzed 27 peer-reviewed studies addressing either or both domains among LGBTQ+ university students. Only 22% of studies integrated mental health and HIV prevention outcomes. These dual-focus programs typically combined trauma-informed counseling, peer-led support, and digital PrEP navigation, yielding reported reductions in depressive symptoms (19–33%) and increased HIV testing or PrEP uptake (17–31%). Interventions using telehealth delivery and self-testing kits showed the highest adoption (≥80%) and maintenance (≥60%) rates.

Fewer than 10% of included studies were based in rural or Appalachian institutions, highlighting a critical equity gap. To assess translational potential, the RE-AIM framework was applied to evaluate reach, effectiveness, adoption, implementation, and maintenance. The MAP-IT model informed planning strategies for institutional scaling and capacity building. Additionally, the Minority Stress Theory and the Social Ecological Model contextualized stigma and structural exclusion as key barriers.

Findings support a public health implementation model focused on digital access, peer engagement, and stigma reduction. This review contributes to SYNC 2026’s call for integrated innovation by identifying scalable, equity-driven interventions that can address co-occurring epidemics affecting LGBTQ+ student populations, particularly in underserved campus communities.