Federal Grant Award Summary

Thomas Jefferson University (Sidney Kimmel Medical College) received a $723,388 Project Grant from the National Institute on Drug Abuse under the Drug Use and Addiction Research Programs (CFDA 93.279) awarded May 15, 2026, with completion targeted for March 31, 2031. The research investigates a novel mechanism regulating central nervous system (CNS) viral load and HIV reservoir formation in the context of substance use, specifically examining how cocaine exposure affects HIV transcription and persistence in microglia—the primary HIV reservoir in the brain. The project will deliver fundamental biomedical research utilizing brain organoids harboring microglia to explore the role of DNA-dependent protein kinase (DNA-PK) in transcription-coupled repair processes and how DNA-PK inhibitors might therapeutically reverse cocaine-enhanced HIV replication in antiretroviral therapy-treated individuals.

The research addresses a critical knowledge gap regarding how DNA-PK-mediated transcription-coupled repair mechanisms function during HIV transcription within microglia under conditions of antiretroviral therapy and cocaine exposure. By elucidating these molecular pathways and testing the therapeutic potential of clinically validated DNA-PK inhibitors, this project aims to contribute new approaches for limiting HIV persistence and associated neuroinflammatory comorbidities in people with HIV experiencing concurrent substance use disorders—a population experiencing significant health disparities from comorbid HIV infection and cocaine use.