Rutgers and Weill Cornell Medicine Win $3 Million to Study HIV’s Toll on the Brain

Antiretroviral drugs let people with HIV live full-length lives, but cognitive problems often persist. Some studies have found cognitive impairment in as many as half of people receiving antiretroviral therapy, although estimates vary and many cases do not interfere with daily activities.

As part of its ongoing efforts to understand and eradicate these effects, the National Institute of Mental Health awarded Rutgers Health and Weill Cornell Medicine $3 million to create a new research enterprise, the New York-New Jersey Center for Actionable NeuroHIV Biomarkers.

"HIV reaches the brain within days of infection, often before people even know they have HIV. And once it gets there, it can persist even after treatment begins, hiding in the DNA of infected cells where antiretroviral drugs can't reach it," said center co-director Tricia Burdo, who also is the associate director of the Rutgers Institute for Translational Medicine and Science and Henry Rutgers Endowed Professor of Translational Medicine.

Infected cells release toxic viral proteins, and ongoing low levels of replication occur despite the drugs. Before antiretroviral therapy, the result was more severe brain damage. With treatment, the effects tend to be milder, but they still impair memory, decision-making, mental health and, in severe cases, the ability to hold a job.

"There are still no effective therapies that specifically prevent or mitigate ongoing brain injury," said the center's other co-director, Lishomwa Ndhlovu, the Herbert J. and Ann L. Siegel Distinguished Professor in Medicine in the Division of Infectious Diseases at Weill Cornell, Cornell University's medical school. "Our goal is to close this critical gap by defining the mechanisms of brain injury and identifying new opportunities for targeted intervention."

Even among those who suffer brain health disorders from HIV, the disease affects different patients differently. Some people lose memory, others lose executive function, and others develop depression or motor problems. The center will combine genomic, protein and clinical data with machine learning to identify biomarkers that distinguish people who suffer from different symptoms and point to the mechanisms driving each.

"If we can identify a subgroup of people with certain cognitive phenotypes such as memory impairment or loss of cognitive function and find a biomarker that tracks with that phenotype, we can then ask what mechanism is driving it and, ultimately, how to target that mechanism with treatment," said Burdo, a professor at Rutgers Robert Wood Johnson Medical School. "That's the path toward a more personalized approach to treatment."

Rather than paying for a single study, the four-year grant will fund shared infrastructure: multi-omics platforms, machine learning (systems used to combine and analyze different biological datasets, such as genomics, transcriptomics, proteomics, and metabolomics) and cerebral organoids, which are lab-grown clusters of human brain cells in which scientists can observe the virus without using animals. The funding also will provide $20,000 pilot grants to junior faculty and researchers new to HIV.

Pilot funding is limited to Rutgers and Weill Cornell investigators, but researchers anywhere can use the center's expertise and core services.