UF receives $4.7 million to study marijuana's role in immunity among HIV-positive adolescents

HIV experts at UF’s College of Medicine, along with colleagues at the University of South Florida and the University of California, San Diego, have been awarded $4.7 million by the National Institutes of Health to study how the complex interplay between marijuana use and HIV infection can influence the development of neurological disorders in adolescents.

The five-year study will use a multidisciplinary approach that could lead to the identification of novel blood-based biomarkers for tracking how substance abuse alters immune function and the progression of HIV infection in the central nervous system. It may also provide evidence to support behavioral guidelines for HIV-infected youth.

“Findings from this study could translate into better diagnosis tools and new therapies to improve long-term outcomes for young adults infected with HIV,” said principal investigator Maureen Goodenow, Ph.D., the Stephany W. Holloway university chair in AIDS research and professor of pathology, immunology and laboratory medicine in the UF College of Medicine.

The work, funded through the National Institute on Drug Abuse, is also a project of the Florida Center for AIDS Research, which is seeking NIH designation as a center of excellence for HIV/AIDS research.

Despite powerful new therapies that have rendered HIV less deadly, movement and cognitive problems, including dementia, are still common among people who are infected. As a result, many infected adolescents may face a lifetime of impaired thinking and behavior.

Marijuana and other drugs also have powerful effects on cognition, so their use by HIV-infected youth could compound the adverse neurological effects associated with the disease. Cannabinoids, the major component of marijuana responsible for the drug’s mind- and mood-altering effects, are associated with suppression of the immune system. But little is known about just how those compounds exert such influence, or how they affect antiretroviral therapy effectiveness and patient outcomes. The researchers will focus on marijuana’s main psychoactive component, a compound called THC that targets receptors produced in the brain, central nervous system and immune system.

The researchers previously found that 30 percent to 40 percent of HIV-infected youth use marijuana, alcohol, cocaine, methamphetamines or other substances, and almost one-third use marijuana every day.

“No one knows whether that is good, bad or indifferent in terms of their disease progression,” said co-principal investigator John Sleasman, M.D., the Robert A. Good professor and chief of pediatric allergy, immunology and rheumatology at the University of South Florida College of Medicine. “We don’t really know what to tell youth in terms of lifestyle management if they have HIV.”

To tackle that problem, the researchers will use a novel cross-disciplinary three-pronged approach to study the varied and overlapping effects of HIV infection and marijuana on the immune system and the central nervous system.

UF virologists will study HIV-infected and HIV-free macrophages — white blood cells that direct the immune system’s response — using a technique called systems biology. That will allow identification of specific cellular changes and interactions related to the active compounds in marijuana. The process generates large amounts of molecular-level data that give an overall picture of how the marijuana compounds affect gene expression and all the proteins thus produced. Pediatric neuropsychologist Sharon Nichols, Ph.D., of UCSD will lead in-depth assessments of memory, motor function, thought process and cognitive reasoning to study the effects of HIV on the brain. And USF neurobiologists will explore the effect of cannabinoids on the immune system, at the basic science level.

Study participants from 16 to 25 years old will be recruited from 15 sites around the country through the National Institute of Child Health and Human Development Adolescent Trials Network, of which USF is a member. Four different groups of individuals who reflect a wide cross section of age, gender, ethnic heritage and sexual orientation will be studied: youth who are already taking antiretroviral therapy, others who are untreated because they do not meet department of health treatment guidelines, some receiving treatment earlier than recommended, and a control group of individuals not infected with HIV.

Overall, the study’s findings could give insight into how behavioral choices affect HIV disease progression and risk for transmission in young adults, and yield clues about the best stage at which to start treatment with antiretroviral drugs.

“The question we’re trying to answer,” Sleasman said, “is ‘how do we best advise these young adults about managing their disease?”