Project Grant R01AI184285

This Project Grant award from the National Institute of Allergy and Infectious Diseases (NIAID), under the Allergy and Infectious Diseases Research program (CFDA 93.855), will provide $694,301 to The Trustees of the University of Pennsylvania to define the mechanisms underlying the protective outcomes observed in the ECLEAR clinical trial. The overarching goal is to understand how early intervention with the broadly neutralizing antibody 3BNC117 at antiretroviral therapy (ART) initiation can enhance CD8+ T cell immunity and enable viral control in individuals infected with 3BNC117-sensitive HIV-1 strains. The research will involve three integrated aims: 1) characterizing the phenotypic, functional, and transcriptomic features of the adaptive T cell immune responses modulated by 3BNC117 treatment, 2) defining how the HIV reservoir is differentially impacted in post-therapy viral controllers versus non-controllers who received 3BNC117, and 3) evaluating the ability of CD8+ T cells from ECLEAR participants to mediate viral control in a humanized mouse model. The anticipated outcomes are a comprehensive understanding of the immunologic and reservoir features associated with the partial efficacy of the ECLEAR trial, as well as validation of the underlying mechanisms to guide future clinical interventions at ART initiation.