Mechanisms of HIV Neuropathogenesis Program

Overview

This program supports research focused on understanding the pathogenic mechanisms involved in HIV-1-associated central nervous system (CNS) dysfunction worldwide. HIV-1 enters the CNS in the acute stages of infection and, despite antiretroviral therapy (ART), a significant proportion of people with HIV develop mild to moderate CNS impairments. This program encourages both basic and clinical research to better understand the factors, mechanisms and pathways involved in the pathogenesis of HIV-1-associated CNS dysfunction. Further, the program encourages the use of state-of-the-art approaches derived from the fields of molecular biology, neurophysiology, neuroimaging, virology, neurology, immunology, neuropsychology, and epidemiology.

Areas of Emphasis

• Basic research on HIV-1-associated CNS dysfunction focusing on neuronal receptors, neural activity, neuronal circuits and networks, and synapto-dendritic damage using models with clinically relevant outcomes.
• Clinical studies to adapt existing diagnostic neuroimaging, other imaging technologies, and electrophysiology-based methods to study neuronal networks and circuits that are specifically compromised in HIV-1 induced CNS dysfunction.
• Clinical Studies to understand the heterogeneity of CNS complications in people with HIV that employ quantitative assessments linked to psychopathology.
• Understand the mechanisms and pathways that modulate patterns of HIV-1 associated CNS symptomatology by deconstructing the multimodal readouts of CNS impairments observed in the setting of suppressive ART.
• Examine the role of factors such as biological sex, gender, cognitive reserve, chronicity of infection, aging, vascular disease, viral reservoirs, co-infections, legacy effects, and coexisting psychiatric conditions in HIV-1 associated CNS dysfunction.
• Develop newer assessment practices including but not limited to computerized assessments, biological markers, and advanced neuroimaging techniques to obtain more consistent diagnoses of HIV-1 associated CNS dysfunction.
• Identify molecular and cellular mechanisms underlying neurological impairment in both acute/early HIV-1 infection and chronic HIV-1 infection.
• Assess the impact on early initiation of ART on long term neurological outcomes across the lifespan.

Contact

Vasudev R. Rao, M.B.B.S., M.S.
5601 Fishers Ln, Room 9G27
Rockville, MD 20852
240-669-5609, vasudev.rao@nih.gov