A major contributor to HIV persistence despite antiretroviral therapy (ART) is latent infection in long-lived CD4+ cell populations. Subsets of these cells have been shown to harbor virus and activate to re-establish infection when ART is stopped. Classification of discreet cell types and the mechanism by which reservoirs are maintained has been limited by lack of access to these cells, which are found in very small numbers in circulating blood. A few groups have been able to isolate cells from gut-associated lymphoid tissues and inguinal lymph nodes, but the yields are often low, and it is unclear if cells in these tissues are representative of the vast majority of cells that reside in other lymphoid tissues. The lack of a safe and accurate method of sampling relevant cell populations in infected individuals has been identified as a key obstacle in advancing the cure agenda. This proposal is a multi-disciplinary effort between physicians and engineers at Stanford University and UCSF to develop a safe and reproducible method for sampling discreet cell types directly from circulating lymph. In Aim I we will develop a clinical protocol for minimally invasive thoracic duct access and sampling. In Aim II we will recruit ten HIV+ patients on HAART from the UCSF SCOPE cohort for lymph and peripheral blood sampling at Stanford University. In Aim III collected samples will be studied using flow cytometry, viral RNA and DNA analysis, and ELISA at UCSF to determine reservoir cell type and compartment. Comparisons will be drawn between lymph and peripheral blood and across different subjects.