Novel Preclinical Models of NeuroHIV with CART

Despite the effectiveness of antiretroviral therapies (ART) in reducing systemic HIV viral loads, central nervous system (CNS) dysfunction remains prevalent in 30-50% of people living with HIV (PWH). ART does not eliminate viral reservoirs in the CNS, leading to chronic neuroimmune dysfunction and conditions like HIV-associated neurocognitive disorder (HAND). Current preclinical research has primarily focused on models that simulate acute HIV infection, but there is a pressing need for models that accurately reflect CNS dysfunction in the context of chronic ART-suppressed infections. Recent advancements in immunodeficient mouse models with humanized immune systems have shown promise, allowing for natural HIV infection and crossing of the blood-brain barrier. These models have provided insights into HIV infection in the CNS and the role of human microglia cells. However, significant gaps remain, particularly in developing models that incorporate multiple human CNS cell types and accurately represent chronic infection dynamics. This proposal aims to develop preclinical NeuroHIV models that better mimic CNS-immune interactions in general and in particular during ART suppression. Specifically, our goal is to develop the next generation NeuroHIV model composed of autologous peripheral human immune cells, relevant human glial cell types, and an intact blood-brain barrier all in the context of ART-mediated HIV suppression. Project Number: 1R61MH143792-01 | Fiscal Year: 2026 | NIH Institute/Center: National Institute of Mental Health (NIMH) | Principal Investigator: J. Victor Garcia-Martinez (+2 co-PIs) | Institution: UNIVERSITY OF ALABAMA AT BIRMINGHAM, BIRMINGHAM, AL | Award Amount: $1,809,036 | Activity Code: R61 | Study Section: Special Emphasis Panel[ZNS1 SRB-U (08)] View on NIH RePORTER: https://reporter.nih.gov/project-details/11239392