A researcher at Case Western Reserve University School of Medicine has been awarded $3.9 million to determine if the combination of the human immunodeficiency virus (HIV) and drug abuse is a double kick in the gut, leading to organ damage throughout the body.
Alan D. Levine, Ph.D., a professor of medicine, molecular biology and microbiology, pathology and pharmacology, is one of five scientists nationwide to receive the competitive 2015 National Institute on Drug Abuse Avant-Garde Award for HIV/AIDS Research. In addition to the $2.5 million Avante-Garde Award, the National Institutes of Health is granting $1.4 million for indirect costs of the project.
Levine recently found that HIV patients--even patients where viral replication is controlled--suffer from leaks in the gastrointestinal tract lining that allow snippets of bacteria normally contained in the bowels to slip into the bloodstream and cause systemic inflammation. Other researchers have shown that methamphetamine, cocaine and opiate abuse damage the same lining.
With this grant, Levine and colleagues will investigate whether gut leakage leads to the disease and malfunction of vital organs commonly found in HIV patients, whether drug abuse exacerbates the problem, how to fix the leaks and whether gut repair improves overall health.
"No one has ever said, 'Let's treat HIV by repairing the bowel,'" Levine said. "But this award is designed for more innovative thinking."
Avant-Garde awards support innovation that may lead to groundbreaking opportunities for prevention and treatment of HIV/AIDS in illicit drug users.
Levine will team with other researchers at Case Western Reserve, The University of British Columbia, the National Institutes of Health, Emory University and the University of Calgary.
"We'll test the theory that pieces of the cell wall, DNA and flagella from gut bacteria enter the bloodstream due to the leaky gut in HIV and trigger systemic inflammation that, in turn, makes the brain, heart, liver, kidney and other organs vulnerable to degenerative diseases and cancers," Levine said.
Levine believes that failure in the gut wall may account for why HIV patients, even those whose virus is well controlled by antiretroviral drugs, commonly suffer these non-AIDS complications.
The group will investigate whether the virus and drug abuse together contribute to more gut damage.
Next, they'll try to determine whether they can repair the bowel, and if such repairs improve patients' overall health.
Initially, investigators will try to identify which biological systems are failing that result in gut leakage and whether they can fix the system or systems and return the lining to healthy function. They'll focus on cytokines, proteins that participate in communication between cells in the immune system; and morphogens, proteins involved in the growth and differentiation of the cells that line the gut.
Alternatively, they'll explore methods to directly heal and maintain a healthy gut lining.
Levine is now retooling his lab to focus on this project. He and his co-researchers will begin their studies in March, when they receive their first of five annual $500,000 payments to support their work.