In response to RFA-AI22-024 Limited Interaction Targeted Epidemiology: Viral Suppression (LITE-VS), we propose “Exploring, Predicting, and Intervening on Long-term Viral suppression Electronically (EPI-LoVE)” with a cross-cutting, interdisciplinary scientific team with strong expertise in longitudinal cohorts to enroll a large, digitally maintained cohort of people living with HIV (PLWH) in the US who are not adequately virally suppressed (>200 copies/mL), report prior gaps in HIV care engagement, or lack of sustained viral suppression (VS). The cohort will investigate trajectories of HIV care engagement and VS applying a theoretical approach and analytic strategies that recognize the cyclical nature of retention in HIV care and VS. We will examine the syndemics underlying these outcomes including substance use, mental health, and barriers to HIV care including stigma and rural isolation. Our strategy includes multiple recruitment methods such as a) social media recruitment in partnership with digital advertising companies employing unique tools, websites/apps and artificial intelligence (AI)-based models to optimize outreach/recruitment; and b) a partnership with AIDS Healthcare Foundation (AHF), the largest HIV medical provider in the country. We will enroll a diverse cohort of PLWH enriched with those living in rural areas, Black, under 25 years of age and experiencing substance use challenges. An evidence-based digital platform (HealthMpowerment, HMP) deployed in 10 studies, including other limited interaction targeted epidemiology (LITE) initiatives, will be used for data collection, real-time analysis and participant communication and will be supplemented with semi-annual blood specimens collected with a multi-pronged strategy (i.e. local laboratory, clinics, and home- based collection options) to facilitate participation. We will develop a sophisticated risk assessment tool to optimize when PLWH in our cohort are most at risk for VNS and deliver tailored, real-time intervention components based on their personalized needs at the time they need them most. Our investigative team from three leading institutions The University of California at Los Angeles and Irvine, and University of North Carolina, Chapel Hill has decades of experience with recruitment, engagement, and care of PLHW and large-scale longitudinal cohort studies, as well as long-standing expertise developing digital and AI-based tools in collaboration with HIV stakeholders. We capitalize upon productive partnerships and expertise to articulate the drivers of the ongoing HIV epidemic among the most vulnerable populations in the US and to identify the most effective, expeditious and scalable digital strategies to address this ongoing public health crisis.