New drug shows promise in clearing HIV from brain
An experimental cancer drug might offer a new way to clear HIV from infected brain cells, according to a recent study by Tulane University. Researchers at the Tulane National Primate Research Center have, for the first time, demonstrated that this drug can significantly reduce levels of Simian Immunodeficiency Virus (SIV)—the primate equivalent of HIV—in the brain. The drug achieves this by targeting and depleting specific immune cells that serve as reservoirs for the virus.
A groundbreaking study published in the journal *Brain* has unveiled a promising new approach to eliminating HIV from hard-to-reach reservoirs, where the virus often evades conventional treatments. This research, led by Dr. Woong-Ki Kim, the associate director for research at the Tulane National Primate Research Center, marks a significant advancement in the fight against HIV-related complications in the brain.
Dr. Kim emphasized the importance of this discovery, stating, "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."
While antiretroviral therapy (ART) has revolutionized HIV treatment by maintaining the virus at undetectable levels in the blood, it does not fully eradicate the virus, necessitating lifelong treatment. HIV persists in viral reservoirs, including the brain, liver, and lymph nodes, where it remains beyond the reach of ART. The brain is particularly challenging due to the blood-brain barrier, a protective membrane that prevents many treatments from entering and clearing the virus. Moreover, long-lived macrophages in the brain are difficult to eradicate once infected.
HIV infection of macrophages contributes to neurocognitive dysfunction, affecting nearly half of those living with HIV. Addressing the virus in the brain is essential for comprehensive HIV treatment and could greatly enhance the quality of life for those with HIV-related neurocognitive issues.
In this study, researchers focused on macrophages, a type of white blood cell that harbors HIV in the brain. They employed a small molecule inhibitor, BLZ945, to block a receptor that increases in HIV-infected macrophages. This strategy effectively reduced the viral load in the brain, suggesting that BLZ945 could clear the virus from brain tissue and offer a new treatment avenue for HIV.
BLZ945, previously studied for amyotrophic lateral sclerosis (ALS) and brain cancer, had not been explored in the context of HIV treatment until now. This innovative approach could represent a significant leap forward in eradicating HIV from the brain, addressing one of the most formidable challenges in HIV treatment.
The study conducted at the Tulane National Primate Research Center involved 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 the small molecule inhibitor for 30 days. The high-dose treatment resulted in a significant reduction in cells expressing HIV receptor sites and a 95-99% decrease in viral DNA loads in the brain.
In addition to lowering viral loads, the treatment did not significantly affect microglia, the brain's resident immune cells crucial for maintaining a healthy neuroimmune environment. Furthermore, no signs of liver toxicity were observed at the doses tested.
The research team plans to next test this therapy in combination with antiretroviral therapy (ART) to evaluate its efficacy in a combined treatment approach. This could lead to more comprehensive strategies for eradicating HIV from the body.
This research was funded by the National Institutes of Health, with grants from the National Institute of Mental Health and the National Institute of Neurological Disorders and Stroke. It was also supported by resources from the Tulane National Primate Research Center base grant of the National Institutes of Health, P51 OD011104.
