Federal Grant Award Summary

The National Institute of Mental Health (NIMH) awarded a $787,498 Project Grant to the University of California, Los Angeles (UCLA) effective July 1, 2026, through March 31, 2031, under the Mental Health Research Grants program (CFDA 93.242). The research initiative, titled "Characterization of HIV Persistence and Neuroinflammation in the CNS Reservoir In Vivo," investigates the mechanisms by which human immunodeficiency virus (HIV) persists in central nervous system (CNS) reservoirs despite effective combination antiretroviral therapy (ART). The project addresses a critical gap in understanding how infiltrating T cells contribute to viral persistence and chronic neuroinflammation in the CNS, conditions that hamper clinical outcomes in people with HIV.

UCLA will employ an integrated research approach utilizing barcoded HIV tracking systems, spatial transcriptomics, single-cell RNA sequencing, and integration site analysis within a novel humanized mouse model to characterize viral reservoirs and define T cell-mediated mechanisms of persistence and inflammation in the CNS. This research builds upon preliminary findings demonstrating robust infection establishment in peripheral and CNS tissues with upregulated Type I interferon signaling, and prior non-human primate studies showing that HIV-specific chimeric antigen receptor (CAR) T cells derived from genetically modified hematopoietic stem/progenitor cells (HSPCs) can traffic to the CNS and reduce viral burden. The findings are intended to optimize CNS reservoir-targeted therapies and inform strategies for delivering therapeutic antiviral T cells to address HIV-associated neuropathogenesis.