Abstract This proposal is highly innovative because it makes available unique resources of the NIH Clinical Center and intramural NCI programs to the only national and international Martin Delaney Collaboratory (MDC), the Pediatric Adolescent Virus Elimination (PAVE) MDC dedicated to pediatric HIV cure research. NIH-PAVE collaboration leverages expertise and networks in PAVE to identify obstacles to protocol participation in groups currently under- represented in cure research in the U.S., to recruit such individuals into studies at the JHU and the NIH Clinical Center, to perform in-depth reservoir characterization with novel tools and to aid with recruitment into studies of HIV cure. It represents the first nationwide protocol to recruit young adults with perinatal HIV infection to study HIV reservoirs using contemporary immunologic and virologic techniques and will establish a registry for long-term evaluation of facilitating future research. The study will conduct new sampling features and combined immunologic/virologic approaches to characterize the reservoir and rebound viremia. Once established, ongoing research studies can be supported through existing mechanisms at PAVE and intramural clinical programs (Maldarelli) and laboratories (Kearney, Maldarelli). There are already several similar longitudinal studies of HIV infection in adults have been ongoing for over 25 years at NIH (e.g. NIH 97-I-0072/08-I-0221 Maldarelli, current PI; 88-I-0172, Wright current PI), and have provided invaluable clinical data and samples for seminal achievements in understanding the long-term effects of ART and the sources of HIV persistence and clonal expansion, as barriers to HIV cure.