UC San Diego receives $12.3 million grant to study the intersection of HIV and methamphetamine use

UC San Diego has received a $12.3 million, five-year grant from the National Institute on Drug Abuse (NIDA), part of the National Institutes of Health (NIH), to launch the Brain-Focused Research on Antiretrovirals and Methamphetamine (Brain-FRAMe) program, a multidisciplinary initiative focused on improving the clinical care and brain health of people with HIV who also have an active methamphetamine use disorder.

Methamphetamine use presents a critical public health challenge, as it significantly increases the risk of HIV infection and complicates the management of the virus. 

“Because it is a stimulant, users may lose their judgment and engage in risky behaviors,” said co-investigator Igor Grant, MD, professor of psychiatry at UC San Diego School of Medicine and director of the HIV Neurobehavioral Research Program. “The drug also changes some immune mechanisms in a way that makes infection more likely.”

Disruption of the blood-brain barrier

For those living with HIV, continued methamphetamine use often leads to severe medical, neurological and mental health disorders. These conditions frequently disrupt the blood-brain barrier and alter immune responses, impairing cognition, mood and impulsivity. Consequently, many individuals find it difficult to adhere to traditional oral antiretroviral therapy (ART), hindering their ability to achieve durable viral suppression.

“There are people who are going to continue to use methamphetamine and who have HIV infection, and who typically have not been included in care, or who have been very difficult to maintain in care, and have been excluded from research,” said Grant. “ We want them to get treatment. This study addresses a population that nobody has addressed before.”

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The Brain-FRAMe program aims to do this by leveraging recent advancements in medical treatment. The program will investigate the combined efficacy of long-acting injectable ART (LAI-ART) and medication for addiction treatment (MAT) with long-acting injectable naltrexone oral bupropion, instead of oral daily pills — the more typical approach. This combination is expected to improve viral suppression and reduce methamphetamine use, providing a vital opportunity to study and restore brain health in this highly vulnerable population.

“Within the five years of the study, we aim to improve the clinical care and brain health of people with HIV and active methamphetamine use by embedding ourselves within and collaborating closely with the HIV-care Owen Clinic here at UC San Diego, which is trying to engage the patients in care, support them through their care and at the same time leverage that to study how this affects brain health,” said contact principal investigator Mariana Cherner, PhD, professor of psychiatry at UC San Diego School of Medicine. 

A multi-disciplinary approach

To achieve this goal, the Brain-FRAMe team has developed a multidisciplinary framework integrating implementation science, pharmacology, virology, immunology and neuroscience. The program is organized into four specialized teams studying the same participants over a 52-week period:

• Clinical Implementation Team: Focused on deploying and evaluating the use of LAI-ART and MAT within the primary care HIV clinic.
• Neurobehavioral Phenotyping Team: Tasked with characterizing the psychiatric, neurocognitive and neuromedical changes resulting from these treatments.
• Biophenotyping and Pharmacology Team: Assessing the effects of methamphetamine and MAT on how the body processes antiretroviral therapies and other medications, and analyzing blood and the cerebrospinal fluid for hidden reservoirs of the virus. 
• Basic Science Mechanisms Team: Investigating the underlying biological drivers of brain dysfunction and repair, including how cellular metabolic pathways regulate immune cell activity, inflammation, and what maintains the integrity of the blood-brain barrier.

Data from these teams will be synthesized by a dedicated Data Integration and Analysis Group to ensure a holistic understanding of the treatment’s impact.

“Collaboration is really at the crux of this program’s success — having experts from different institutions and different departments within UC San Diego come together and converge on these issues,” said Cherner. 

The Brain-FRAMe program represents a pivotal shift in how researchers approach the intersection of substance use and HIV care, according to the team. By addressing the biological mechanisms of brain health alongside clinical treatment, it could create a blueprint for transforming quality of life for people living with HIV and methamphetamine addiction and ultimately reduce new infections and advance public health outcomes in the San Diego community and beyond.