There are 38 million people living with HIV (PLWH) worldwide, 68% of whom live in sub-Saharan Africa. With the transition of HIV from an acute illness to a chronic condition, co-morbid non-communicable diseases (NCDs) such as depression and anxiety disorder, alcohol use disorder (AUD), and hypertension (HTN) have become epidemic among PLWH. Despite evidence-based interventions to promote integration of these HIV comorbidities into HIV service delivery, integration efforts face challenges. First, integration commonly fails to recognize the syndemic relationships between these conditions and the deleterious effect of social factors such as poverty, stigma, and lack of access to care that worsen their outcomes, especially in low- and middle-income countries. Second, integration commonly imposes additional clinical tasks upon overburdened healthcare workers (HCW) operating in busy clinical environments without private space needed to attend to these additional conditions that are often stigmatized. A syndemic approach, which explicitly integrates the biological and social interactions that cause these conditions to cluster, has been proposed as a means of addressing the complex needs of PLWH. Mobile health (mHealth), an evidence-based strategy that leverages the widespread penetration of mobile phones to relieve HCW of burdensome tasks while enabling their systematic, consistent implementation, has been proposed as a solution to address HIV-related syndemics, but this approach has not been tested. Our exemplary multidisciplinary team has a strong track record of collaboration. In the current proposal, which leverages the infrastructure of an ongoing implementation study of HIV/HTN integration in Uganda, we will pursue these Specific Aims: Aim 1) Adapt Medly Uganda for detection, linkage to care, and ongoing support of depression, anxiety disorder, and AUD among Ugandans with HIV and HTN using a syndemic approach. Through human-centered design (HCD), we will engage patients, caregivers, and professional/lay HCW to guide iterative adaptation of Medly Uganda with explicit attention to common biosocial drivers. The adapted application will integrate widely used (1) screening instruments along with validated measures of significant life events, economic shocks, and stigma, (2) algorithm-driven messaging and alerts, and (3) linkage to HCW for support and treatment. We will also develop and operationalize a novel syndemic care cascade (R21 phase); Aim 2) Assess the effectiveness of the Syndemic-Adapted Medly Uganda (SAMU) to improve mental health care cascade metrics by conducting a single-arm trial using real-world historical data (R33 phase); Aim 3) Evaluate the factors impacting sustained engagement in the adapted Medly Uganda using mixed methods (R33 phase). Throughout the study period, we will focus on strengthening our Uganda-based team's mHealth research capacity and furthering our partnerships with government officials to ensure that SAMU can be loc...