An experimental medication initially aimed at cancer treatment might assist in eliminating HIV from infected brain cells, reveals a recent study. By specifically targeting these cells, the drug could help eradicate the virus from hidden sites that present a significant challenge in treating HIV.
A new study from Tulane University suggests that an experimental drug designed for cancer treatment could aid in clearing HIV from infected brain cells.
In a pioneering study, scientists at the Tulane National Primate Research Center demonstrated that a cancer medication notably lowered levels of SIV, which is the equivalent of HIV in nonhuman primates, by attacking and eliminating specific immune cells where the virus resides in the brain.
This important finding, published in the journal Brain, represents a significant advance in efforts to eradicate HIV from challenging areas where the virus hides from effective therapies.
“This research represents a crucial advancement in addressing brain-related issues linked to HIV, which continue to affect individuals even when they are on effective HIV treatments,” stated Dr. Woong-Ki Kim, the lead author and associate director for research at the Tulane National Primate Research Center. “By concentrating on infected cells in the brain, we may have the ability to eliminate the virus from these hidden regions, a key challenge in HIV therapy.”
Antiretroviral therapy (ART) is vital for effective HIV treatment, keeping the virus at low levels in the bloodstream and changing HIV from a life-threatening condition to a manageable one. Nonetheless, ART does not fully remove HIV, requiring ongoing treatment. The virus survives in “viral reservoirs” located in the brain, liver, and lymph nodes, where ART cannot reach.
The brain poses a particular obstacle for treatment due to the blood-brain barrier, a protective layer that prevents harmful substances from entering but also inhibits therapeutic agents, allowing the virus to persist. Moreover, macrophages in the brain are exceptionally long-lived, complicating efforts to eradicate them once infected.
Infected macrophages are believed to contribute to neurocognitive impairments, affecting nearly half of all individuals diagnosed with HIV. Eliminating the virus from the brain is essential for comprehensive HIV treatment and could greatly enhance the quality of life for those experiencing HIV-related cognitive issues.
This research focused on macrophages, a specific type of white blood cell that retains HIV in the brain. By employing a small molecule inhibitor to obstruct a receptor that increases in HIV-infected macrophages, the researchers successfully decreased the viral load in the brain. This strategy effectively cleared the virus from brain tissue, opening a potential new pathway for HIV treatment.
The small molecule inhibitor utilized, BLZ945, has been evaluated for its therapeutic potential in conditions like amyotrophic lateral sclerosis (ALS) and brain cancer, but this is its first application in targeting HIV within the brain.
The study, conducted at the Tulane National Primate Research Center, included three groups to simulate human HIV infection and treatment: a control group, and two groups given either a low or high dose of the small molecule inhibitor over 30 days. The high-dose group experienced a significant reduction in cells that express HIV receptor sites and saw a 95-99% reduction in viral DNA amounts in the brain.
Alongside lowering viral levels, the treatment did not considerably affect the microglia, which are the brain’s immune cells essential for maintaining healthy neuroimmune functions. There were also no indications of liver toxicity at the doses examined.
The next phase for the research team is to evaluate this therapy in combination with ART to determine its effectiveness as part of a dual treatment strategy. This could lead to improved methods for completely eradicating HIV from the body.
This study received funding from the National Institutes of Health, including grants from the National Institute of Mental Health and the National Institute of Neurological Disorders and Stroke, and benefitted from resources from the Tulane National Primate Research Center base grant, P51 OD011104, from the National Institutes of Health.
