Background: The rate of HIV has doubled in the last 15 years among young people to 22% of HIV cases. Scientific advances in biomedical HIV prevention strategies have not been utilized by youth. Methods/Design: Young people aged 12 -24 years old (n= 1500) are being recruited from community-based organizations (CBO) and clinics serving gay, bisexual, and transgender youth, homeless youth, youth on probation or released from incarceration, and youth in other high-risk venues (e.g., bars and clubs). Youth are randomized in a factorial design to: 1) an automated messaging and monitoring intervention (AMMI) using text messages (n = 900); 2) AMMI plus peer support via private social media (n = 200); 3) AMMI plus strengths-based coaching (n = 200); and 4) AMMI, peer support, and coaching (n = 200). At four-month intervals over 24 months, interviewers monitor: uptake of the steps in the HIV Prevention Continuum (linkage to health care and adherence to pre-or post-exposure prophylaxis or 100% condom use), and conduct repeat rapid diagnostic tests for HIV, sexually transmitted infections (STI), drugs and alcohol use. Weekly automated monitoring via text (or email) in AMMI includes questions on acute HIV and STI symptoms for immediate follow-up by interviewers to provide HIV and STI testing, STI treatment, and partner therapy. Discussion: The greatest impacts are expected among youth receiving the most intensive intervention (i.e., AMMI, peer support, and coach). However, the youth's concurrent mental health, substance abuse, and housing and food security are expected to be significant covariates that influence the uptake of the HIV Prevention Continuum. This study operationalizes the guidelines of the Centers of Disease Control and Prevention (CDC) regarding the prevention of HIV among the highest risk youth, using community-based point of care diagnostics supported by scalable technology-mediated interventions. Similarly, over 90% of adolescents under age 18 go online daily, more than half several times a day which is facilitated by access to smartphones among 75% of youth of each ethnicity, crossing the digital divide [28]. Much of this online activity is driven by social media use, particularly via smartphones -for example, over 70% of adolescents under 18 years use Facebook, while about half also use Instagram and Snapchat [28]. The interventions in this study use text messaging and social media to engage "youth where they are" in the digital environment. This approach has resulted in four intervention arms which vary in intensity and costs. In order of increasing intensity and costs, the interventions are: 1) automated text-messaging and weekly monitoring probes; 2) peer support via social media; 3) paraprofessional coaching; and 4) all three combined. This study's automated and interpersonally-mediated technology-based interventions will be based on the shared features of existing EBI -we will not create a new app nor an EBI with a manual to be replicated with 6 fidelity [14,33,34]. In the last 25 years, over...