Project Summary Pre-exposure prophylaxis (PrEP), in which persons with ongoing HIV risk use antiretroviral medications to reduce their risk of acquiring HIV infection, is a promising prevention strategy. However, data show that PrEP’s effectiveness is greatly compromised by suboptimal adherence to treatment.1 Persons on PrEP face many challenges to optimal adherence and retention in care, including stigma and misperceptions about risk.2,3 Due to these challenges, the prescribing of PrEP should be accompanied by adherence interventions that are appealing to diverse populations.1,4 We developed and examined the preliminary efficacy of an action-oriented, appealing, mobile game to improve adherence to PrEP entitled Viral Combat.5,6 Viral Combat was tested in a randomized trial with 69 participants newly initiating PrEP. At the 24-week follow-up, those in the intervention group were 3.75 times (p=0.02) as likely to engage in optimal PrEP dosing (i.e. 4 or more days/week as indicated using levels of tenofovir diphosphate from dried blood spots) compared to the control group.6 In this next phase of research, we will test Viral Combat through a multisite Hybrid Type 1 effectiveness- implementation randomized controlled trial (RCT) with 200 participants ages 15-34 years, receiving PrEP care at clinical sites in the South (n=100 Jackson, MS) and New England (n=100, Providence, RI; Boston, MA). The integrated Promoting Action on Research Implementation in Health Services (i-PARIHS) framework will examine the facilitators and barriers to the intervention’s implementation. Formative interviews with stakeholders will inform this intervention prior to the trial, and post-evaluation interview will summarize issues relevant to future dissemination. 45