Researchers find new way to protect the brain from HIV and opioid damage

People living with HIV continue to struggle with memory loss, difficulty concentrating and poor decision-making, even as antiretroviral treatments have dramatically improved life expectancy. For patients who also use opioids—which may be prescribed to manage the chronic pain that can accompany HIV—these cognitive problems can be even worse. Until now, scientists haven’t understood exactly why.

Texas A&M Health researchers say they’ve uncovered a key factor in HIV- and opioid-use-related cognitive impairment—and it could point to a promising new way to protect the brain. In a new study, published in Cell Death and Disease, a Nature Portfolio journal, the research team revealed that HIV and opioids combine to disrupt the brain’s natural DNA repair system. This damage leads to ongoing inflammation and cognitive impairment. But the researchers believe an existing drug, approved by the Food and Drug Administration (FDA), might help reverse the effects.

Cracking the code of brain decline

People living with HIV are more likely to experience chronic pain than the general population. Between 21% and 53% are prescribed opioids to manage pain associated with HIV, aging or the side effects of other medications. Opioids also intersect with HIV through injection drug use. Sharing needles or other injection equipment when using opioids such as heroin can transmit HIV, contributing to the overlap between the two conditions.

Dr. Karthick Chennakesavan, the study’s first author and assistant research scientist at the Texas A&M University Irma Lerma Rangel College of Pharmacy at Texas A&M Health, said the combination of HIV and opioids is more than just the sum of their individual effects.

“Our findings show that HIV and opioids don’t just pile onto inflammation independently—they actually change the way the brain works at its most basic level,” Chennakesavan said. “By finding out how this happens, we hope to create new treatments that keep brains healthier longer.”

It’s long been known that HIV can cause neurological problems, and opioid use can magnify them. But until now, the underlying mechanisms were unclear. To solve the puzzle, Dr. Samikkannu Thangavel, associate professor at the Rangel College of Pharmacy who led the research team, and his colleagues examined lab-grown microglia (immune cells of the brain), genetically modified mice carrying selected HIV genes, and postmortem brain tissues from people who lived with HIV.

They discovered that the HIV protein Tat (trans-activator of transcription) and morphine (a potent opiate) work together to trigger the brain’s response to DNA damage while disrupting the cellular processes that organize and repair DNA. Morphine further amplified these effects, contributing to ongoing DNA damage, changes in epigenetic markers and the activation of immune pathways. Together, these changes contributed to chronic inflammation and impaired nerve function.

“When HIV and morphine combine, the brain becomes stuck in a cycle of ongoing DNA damage and inflammation,” Chennakesavan explained.

A drug with hope for the future

Once the researchers understood this damaging cycle, they wondered whether it could be reversed. They tested dimethyl fumarate (DMF), a medication that is already approved to treat multiple sclerosis and is known for its anti-inflammatory and brain-protecting properties.

The results were striking: DMF restored the brain’s organization for repairing DNA, calmed harmful immune signaling and improved signs of brain health in laboratory models. Similar positive effects appeared after altering related DNA repair signals.

“What’s exciting is that DMF targets the root problem—restoring the brain’s natural repair ability—instead of just tamping down inflammation after the damage is done,” Thangavel said.

Why it matters

As more people live longer with HIV, keeping their brains healthy becomes a top priority. Furthermore, millions worldwide face not just the challenge of HIV itself, but also added risks from opioid use disorder. This new research connects the dots between HIV, opioids, DNA damage and brain inflammation, suggesting that therapies targeting DNA repair could offer a promising approach beyond current strategies.

“This work gives us a new way to look at HIV-related brain disease,” Thangavel said. “Since dimethyl fumarate is already approved for other uses, it’s a promising candidate for testing in people with HIV-associated cognitive problems.”

Next steps

The Texas A&M team, with collaborators from the University of Florida and Harvard Medical School, is now expanding their research. They aim to identify early warning signs of DNA damage, test these findings in human tissue and explore new drugs—including DMF—for preserving cognitive function in HIV patients, especially those who use opioids.

“Our ultimate goal is to stop brain decline before it becomes permanent,” Thangavel said. “By tackling the root cause of inflammation, we believe millions of people aging with HIV could have a better quality of life.”

By showing how HIV and opioids work together to disrupt DNA repair, this study moves beyond treating inflammation itself—it opens the door to therapies that fix the problem where it starts.

Funding for the research came from the National Institutes of Health, the National Institute on Drug Abuse and Texas A&M University. The team includes scientists from Texas A&M, the University of Florida and Harvard Medical School.

By Shelby Purdy, Texas A&M Health

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ABOUT THE RANGEL COLLEGE OF PHARMACY

In 2006, the Texas A&M University Irma Lerma Rangel College of Pharmacy opened its doors in Kingsville, Texas, to address the critical shortage of pharmacists in the South Texas community. Following growth, it expanded to the College Station campus in 2014 and now offers its PharmD and PhD programs to students on both campuses. Its mission is to develop and inspire a diverse group of future leaders in pharmacy practice and pharmaceutical sciences through transformational education, innovative research, holistic care and effective outreach and service. The institution has earned full professional accreditation and garnered recognition as one of the top 50 pharmacy programs in the nation. Learn more at pharmacy.tamu.edu.

ABOUT TEXAS A&M HEALTH

Texas A&M University Health Science Center (Texas A&M Health) comprises five colleges and schools (dentistry, medicine, nursing, pharmacy and public health), integrated University Health Services, several research centers and institutes, and numerous outpatient clinics with a shared mission of advancing health care for all. We serve the state and beyond with campuses and locations in Bryan-College Station, Dallas, Houston, Round Rock, Kingsville, Corpus Christi, McAllen and Navasota. Learn more at health.tamu.edu or follow @TAMUHealth on X (née Twitter).

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