Substance use disorders (SUDs) and depression in HIV-infected patients result in poor HIV outcomes, yet are often unrecognized and untreated. To address these problems, this study examines the implementation and effectiveness of a clinical intervention consisting of self-administered tablet-based SUD and depression screening at routine HIV primary care clinic visits, followed by evidence-based treatments for SUD and depression delivered by a behavioral health specialist. If successful, this study has potential to reduce SUD- and depression-related problems and reduce HIV treatment disparities for patients with these comorbidities.