BACKGROUND: Young men who have sex with men (YMSM) are the fastest-growing HIV-positive population worldwide. Thailand has the highest adult HIV seroprevalence in Asia; over 25% of men having sex with men in Bangkok are HIV positive. Pre-exposure prophylaxis (PrEP) is an efficacious HIV prevention strategy recommended for all at-risk individuals. PrEP is highly effective when taken as prescribed, but PrEP utilization rate has been low, and adherence is often inadequate. OBJECTIVE: We propose to develop and pilot a multicomponent, technology-based intervention to promote motivation to begin PrEP ("uptake") and sustained adherence to PrEP among HIV-negative Thai YMSM. We will adapt an existing 2-session technology-delivered, motivational interviewing-based intervention to focus on PrEP use in YMSM in Thailand. The resulting intervention is called the Motivational Enhancement System for PrEP Uptake and Adherence (MES-PrEP). We will also develop motivational text messaging (MTM) to send two-way motivational messages to promote PrEP use. METHODS: The proposed study includes 3 phases. Phase 1 includes in-depth interviews with HIV-negative Thai YMSM and providers to explore barriers and facilitators of PrEP initiation and adherence, aiming to inform intervention content. Phase 2 consists of adapting and beta-testing MES-PrEP and MTM for functionality and feasibility using a youth advisory board of Thai YMSM. In Phase 3, we will conduct a pilot randomized controlled trial to evaluate the feasibility, acceptability, and preliminary efficacy of MES-PrEP and MTM to increase PrEP uptake and adherence among Thai YMSM. A total of 60 HIV-negative Thai YMSM who have not started PrEP and 60 YMSM who are on PrEP but not adherent to it will be randomized 2:1 to receive MES-PrEP and MTM (n=40) or standard PrEP counseling (n=20). The feasibility and acceptability of the intervention will be assessed through usage patterns and the System Usability Scale. The preliminary impact will be assessed by evaluating the proportion of PrEP initiation and level of adherence to PrEP. Participants will complete the assessments at baseline and at 1-, 3-, and 6-month postintervention. Biomarkers of adherence to PrEP and biomarkers of HIV and sexually transmitted infections will be collected. RESULTS: Recruitment for this study began in January 2022 for phase 1. Qualitative interviews were completed with 30 YMSM and 5 clinical providers in May 2022. Phase 3, the pilot feasibility and acceptability trial, began in July 2023. Upon project completion, we shall have developed a highly innovative mobile health intervention to support YMSM using PrEP, which will be ready for testing in a larger efficacy trial. CONCLUSIONS: This study addresses a critical problem (ie, high HIV incidence and low PrEP use) among Thai YMSM. We are developing 2 potentially synergistic technology-based, theory-driven interventions aimed at maximizing PrEP use. The proposed project has the potential to make significant contributions to advancing HIV prevention research and implementation science. TRIAL REGISTRATION: ClinicalTrials.gov NCT05243030; https://clinicaltrials.gov/ct2/show/NCT05243030. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/46435.