Could treating HIV earlier protect the brain from accelerated aging?
Tulane University has received a five-year, $4.2 million grant from the National Institutes of Health to study why people with well-controlled HIV can still experience accelerated brain aging, and whether earlier treatment could help prevent it.
As people with HIV live for decades on effective treatment, preserving long-term brain health is becoming an increasingly important part of HIV care. Antiretroviral therapy, or ART, can suppress the virus to undetectable levels but does not eliminate all of its long-term effects. Even those with well-controlled HIV can experience age-related cognitive changes earlier than people without the virus.
“Suppressing the virus is only part of the story,” said lead study investigator Andrew MacLean, associate professor of microbiology and immunology at the Tulane National Biomedical Research Center. “We want to know whether HIV sets aging-related changes in motion in the brain before treatment begins, and whether treating almost immediately after infection can keep those changes from becoming established.”
The study seeks to identify new therapeutic targets to protect brain health and cognitive function across the lifespan.
MacLean’s team will focus on astrocytes, star-shaped cells that support neurons and help maintain the blood-brain barrier. Researchers suspect that HIV-related inflammation may push some astrocytes into an aging-related state in which cells no longer function normally and can contribute to persistent inflammation and neurodegeneration.
MacLean’s team studies HIV using simian immunodeficiency virus, or SIV, in nonhuman primates. Earlier studies found signs of accelerated aging in brain cells during acute infection. When ART was started later, it reduced some measures of neurodegeneration, but several markers remained.
The new study will test whether starting ART just three days after infection can prevent those effects from taking hold and preserve cognitive function. Researchers will compare very early treatment with treatment begun after the infection is established, tracking inflammation, cellular aging and cognition over time. A separate ART-only group will help distinguish changes caused by the infection from those potentially associated with the medications themselves.
The study breaks new ground in its combined approach, pairing a well-established nonhuman primate model of HIV with advanced molecular, imaging and computational tools. Together, these approaches can show how infection and treatment affect the brain over time, while also pinpointing which cells and pathways are involved, where changes occur in the brain, and how they relate to memory and behavior. This study also draws on existing research archives and uses the same samples for multiple analyses, helping researchers get more information from materials already collected while reducing the number of animals needed.