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Background: Adolescents and young adults (age 13 - 24) accounted for 20% of HIV diagnoses in the United States and 6 dependent areas in 2020. Optimal treatment adherence during adolescence and young adulthood decreases the pool of infectious individuals during the risky sexual activity commonly reported among AYAs living with HIV., Methods: Adolescents and young adults newly recommended to start antiretroviral therapy (ART) were recruited, nationally, from seven clinical sites. At each clinical site, participants were randomized to receive a two-session (baseline and 1- month) online intervention. For the Motivational Enhancement System for Health (MESA) intervention condition, based on the principles of motivational interviewing, participants received ART information and personalized feedback + ART standard of care (n = 86), while for the System for Health (SH) control condition, participants received information on healthy eating and physical activity + ART standard of care (n = 66)., Results: Adherence was 21% greater in the MESA intervention group compared to the SH control group at 6 months. Additionally, the MESA intervention group was significantly more adherent during the post intervention, and was more likely to maintain viral suppression up to 12 months after initiating ART if both doses of the intervention were received compared to the SH control group., Conclusion: A brief, scalable online computer-delivered intervention shows promise for achieving long-term health outcomes due to improved adherence when intervention occurs early in the course of treatment., Competing Interests: The authors report no conflicts of interest related to this work., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)