A groundbreaking study from Tulane University has uncovered a potential new treatment that may help eliminate HIV from one of its most stubborn hiding places – the brain. The research, published in the journal Brain, shows that an experimental drug originally developed for cancer treatment significantly reduced levels of SIV, the nonhuman primate equivalent of HIV, in the brains of infected animals.
Targeting HIV’s Hidden Reservoirs
While current antiretroviral therapy (ART) has transformed HIV from a terminal illness to a manageable condition, it falls short of completely eradicating the virus. HIV persists in “viral reservoirs” in the brain, liver, and lymph nodes, where it remains out of reach of ART. The brain has been particularly challenging due to the blood-brain barrier, which protects the organ from harmful substances but also blocks treatments.
Lead study author Woong-Ki Kim, PhD, associate director for research at Tulane National Primate Research Center, explains the significance: “This research is an important step in tackling brain-related issues caused by HIV, which still affect people even when they are on effective HIV medication. By specifically targeting the infected cells in the brain, we may be able to clear the virus from these hidden areas, which has been a major challenge in HIV treatment.”
The persistence of HIV in the brain is thought to contribute to neurocognitive dysfunction, experienced by nearly half of those living with HIV. Eradicating the virus from this organ is crucial for comprehensive HIV treatment and could significantly improve the quality of life for those affected.
A Novel Approach to HIV Elimination
The Tulane team focused on macrophages, a type of white blood cell that harbors HIV in the brain. They used a small molecule inhibitor called BLZ945 to block a receptor that increases in HIV-infected macrophages. This approach successfully reduced the viral load in the brain, essentially clearing the virus from brain tissue.
The study, conducted at the Tulane National Primate Research Center, used three groups to model human HIV infection and treatment: an untreated control group, and two groups treated with either a low or high dose of BLZ945 for 30 days. The high-dose treatment led to a remarkable 95-99% decrease in viral DNA loads in the brain.
Importantly, the treatment did not significantly impact microglia, the brain’s resident immune cells essential for maintaining a healthy neuroimmune environment. It also showed no signs of liver toxicity at the doses tested.
Why it matters: This research represents a significant step forward in HIV treatment. If successful in humans, this approach could address one of the most challenging aspects of HIV management – clearing the virus from the brain. This could potentially lead to improved cognitive outcomes for people living with HIV and bring us closer to complete viral eradication.
The study’s findings are particularly exciting because they repurpose a drug originally developed for cancer treatment. BLZ945 has previously been studied for therapeutic use in amyotrophic lateral sclerosis (ALS) and brain cancer, but this is the first time it has been applied to clearing HIV from the brain.
However, it’s important to note that this research is still in its early stages. The next step for the research team is to test this therapy in conjunction with ART to assess its efficacy in a combined treatment approach. This could pave the way for more comprehensive strategies to eradicate HIV from the body entirely.
While these results are promising, several questions remain. Will the treatment be as effective in humans as it is in nonhuman primates? Are there long-term side effects that haven’t yet been observed? How will this treatment interact with existing antiretroviral therapies?
As research progresses, the potential impact of this discovery extends beyond HIV treatment. The approach of targeting specific cells in the brain could potentially be applied to other neurological conditions where certain cell types play a key role in disease progression.
This study, funded by the National Institutes of Health, including grants from the National Institute of Mental Health and the National Institute of Neurological Disorders and Stroke, represents a significant step forward in HIV research. It offers hope for more effective treatments and potentially even a cure for HIV in the future.
