Mass cytometry, or CyTOF, is a powerful technology that has been used for comprehensive multiparameter characterization of immune cells. We recently conducted a 38-parameter characterization of HIV entry and productive infection of tissue CD4+ T cells by CyTOF, and used an analytical approach that takes advantage of the high-dimensional nature of CyTOF datasets to distinguish receptors modulated during infection from those differentially expressed on preferentially infected cells. These studies identified a subset of memory CD4+ T cells susceptible to HIV entry but not productive infection. Ongoing work in the lab seeks to characterize the molecular basis of this post-entry restriction, to use CyTOF and a variety of high-dimensional CyTOF data analysis tools to characterize the types of cells that are productively and latently infected with HIV, and to apply the high-dimensional analysis approaches we have developed on HIV-infected cells characterized by single-cell RNAseq. We are also working closely with UCSF’s SCOPE cohort to identify signatures and biomarkers of infected cells that persist in HIV-infected individuals on suppressive antiretroviral therapy, as well as signatures of immune effector cells that can control viral replication in these infected individuals.