PROJECT SUMMARY HIV infection can persist long-term antiretroviral therapy as a reservoir of provirus integrated into host cell genomes. The stability and activity of this reservoir depends on the complex interplay between viral and host mechanisms. The overall goal of this P01 is to characterize the mechanisms of formation, persistence, reactivation, and therapeutic responsiveness of the HIV reservoir in unprecedented detail. This will involve generating high-dimensional and longitudinal single-cell and single-genome datasets. The role of the Data Analytics & Modeling Core is to provide specialized quantitative methods to each of the research projects to aid in the design and interpretation of the experimental studies. The Core will bring together analytical experts contributing to each project to collaboratively plan, conduct, and interpret analyses. Core members will develop and apply state-of-the-art bioinformatic methods to interpret high-dimensional biological data characterizing the HIV reservoir. They will additionally develop and apply mechanistic viral dynamics models to understand the mechanism of reservoir formation, persistence, and reactivation, with the long-term goal of predicting outcomes of novel therapeutics. Overall the Data Analytics & Modeling Core will advance the goals of this program project by building a more complete understanding of the causes and consequences of HIV reservoir dynamics.