Project Summary The overarching goal of this proposal is to better understand the dynamics of HIV-1 persistence in perinatal infection with very early treatment (VET) within 48 hours of life, early treatment by 2-3 months of age combined with long-term suppression, and when initial ART is combined with broadly neutralizing antibodies, to facilitate viral remission. Eliminating the resting memory CD4+ T cell latent HIV-1 reservoir is the major challenge for eradicating HIV-1 from treated individuals. VET and early treatment of perinatal infection leads to a dramatic reduction in HIV-1 reservoir size that may enable sustained HIV-1 remission, but requires additional studies including mathematical modelling of reservoir dynamics. The proposed project will address a critical barrier to assessing HIV remission and cure studies in perinatally infected children and adolescents, with direct application to the rapidly evolving and exciting field of HIV cure. The studies have direct relevance to the research mission of the National Institutes of Health where finding ways to achieve HIV-1 viral remission or cure is a top research priority.