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Background  The past 30 years have witnessed such significant progress in the prevention and treatment of HIV/AIDS that an AIDS-free generation and the end to the global AIDS epidemic are ambitious, but achievable, national and global goals. Despite growing optimism, globally, youth living with HIV are markedly less likely to receive antiretroviral therapy than adults (23% vs 38%). Furthermore, marked health disparities exist regarding HIV infection risk, with young men of color who have sex with men disproportionately affected. A large body of research has identified highly impactful facilitators of and barriers to behavior change. Several efficacious interventions have been created that decrease the rate of new HIV infections among youth and reduce morbidity among youth living with HIV. However, full benefits that should be possible based on the tools and interventions currently available are yet to be realized in youth, in large part, because efficacious interventions have not been implemented in real-world settings.  Scale It Up  (SIU) primarily aims to assemble research teams that will ultimately bring to practice evidence-based interventions that positively impact the youth HIV prevention and care cascades, and in turn, advance the fields of implementation science and self-management science.    Objective  This paper aims to describe the structure of the U19-SIU and the effectiveness-implementation hybrid trials, as well as other center-wide protocols and initiatives, implemented within SIU.    Methods  SIU will achieve its aims through 4 individual primary protocols, 2 center-wide protocols, and 3 cross-project initiatives.    Results  SIU was funded by National Institute for Child Health and Human Development (U19HD089875) and began in October 2016. As of November 2018, 6 SIU protocols have launched at least the first phase of work (ATN 144 SMART: Sequential Multiple Assignment Randomized Trial; ATN 145 YMHP: Young Men’s Health Project; ATN 146 TMI: Tailored Motivational Interviewing Intervention; ATN 153 EPIS: Exploration, Preparation, Implementation, Sustainment model; ATN 154 CM: Cascade Monitoring; ATN 156 We Test: Couples' Communication and HIV Testing). Further details can be found in the individual protocol papers.    Conclusions  To date, the youth HIV research portfolio has not adequately advanced the important care area of self-management. SIU protocols and initiatives address this broad issue by focusing on evaluating the effectiveness and implementation of self-management interventions. SIU is highly innovative for 5 primary reasons: (1) our research framework expands the application of “self-management”; (2) the 4 primary protocols utilize innovative hybrid designs; (3) our Analytic Core will conduct cost-effectiveness analyses of each intervention; (4) across all 4 primary protocols, our Implementation Science Core will apply implementation scales designed to assess inner and outer context factors; and (5) we shall advance understanding of the dynamics between provider and patient through analysis of recorded interactions.    International Registered Report Identifier (IRRID)  DERR1-10.2196/11204

Adolescent Trials Network for HIV-AIDS Scale It Up Program: Protocol for a Rational and Overview