Velpandi Ayyavoo, PhD, professor and vice chair for research in the Department of Infectious Diseases and Microbiology at the University of Pittsburgh School of Public Health, received an R01 grant from the National Institute of Neurological Disorders and Stroke—part of the National Institutes of Health—to investigate the mechanisms contributing to cognitive impairment in people with human immunodeficiency virus (HIV).
The five-year, $2,964,377 grant will fund the project, “HIV Mediated Dysregulation of the CNS Complement System: A Mechanistic Link Between Chronic Neuroinflammation and Cognitive Dysfunction.”
Despite effective suppression of HIV with antiretroviral therapy—the most common treatment for the virus—nearly half of people with HIV experience persistent neurocognitive impairment. Researchers believe this impairment may be driven by chronic immune dysfunction in the brain, even when the treatment prevents the virus from multiplying.
“Antiretroviral therapy has transformed HIV into a manageable chronic condition, but cognitive impairment continues to affect many people living with HIV,” Ayyavoo said. “We want to better understand what continues to drive inflammation and neuronal damage even when the virus itself is well controlled.”
To understand these processes, Ayyavoo and her team will use a vascularized, immune-competent human neurovascular unit brain organoid (NVU-BO) that integrates neurons, astrocytes, microglia, oligodendrocytes, endothelial cells, and pericytes.
Ernesto T. Marques Jr., MD, PhD, associate professor of infectious diseases and microbiology at Pitt Public Health, will serve as a co-investigator on the project.
“This model gives us an opportunity to study these complex interactions in a human brain-like environment and understand not only what is happening, but how it is happening,” said Ayyavoo. “Ultimately, we hope this work identifies new therapeutic targets that can protect brain health and improve quality of life for people living with HIV.”
-Ava Dzurenda