$154,000 NIH grant to enhance HIV treatment by targeting hidden reservoirs of the virus

Ted Cory, PharmD, PhD, associate professor at the University of Tennessee Health Science Center College of Pharmacy, has secured a $154,000 grant from the National Institutes of Health to advance the fight against HIV by focusing on improving how antiretroviral drugs reach hidden reservoirs within the body.

Since the arrival of modern antiretroviral therapy (ART) over two decades ago, outcomes for HIV patients have significantly improved. However, challenges remain in fully eradicating the virus, mainly because HIV can hide in cells like macrophages, which are not the primary targets of current treatments.

Along with his co-investigator, Professor Santosh Kumar, PhD, Dr. Cory’s research aims to investigate and improve drug penetration into these elusive cells, potentially representing a significant step toward increasing HIV therapy effectiveness and moving closer to the goal of complete viral eradication.

Modern antiretroviral therapy has revolutionized HIV treatment. ART manages HIV infection by combining multiple medications that help control the virus and prevent progression to AIDS. While ART does not completely eliminate the virus, it greatly improves the health and well-being of those living with HIV and reduces the risk of HIV transmission. The treatment typically involves taking a regimen of medications, which can be administered daily as pills or through monthly or bi-monthly injections, under medical supervision. This treatment has turned HIV diagnoses from virtual death sentences into a manageable condition for many patients.

HIV primarily targets CD4+ helper T cells, which play an important role in the adaptive immune system by aiding other immune cells. However, HIV can also infect other white blood cells, such as macrophages, which play a crucial role by engulfing and destroying microorganisms, clearing dead cells, and stimulating other parts of the immune system. These cells are not usually the main targets of current ART drugs, allowing HIV to hide and preventing complete eradication.

Dr. Cory’s research aims to improve how HIV medications reach these hidden reservoirs within the body, reducing the virus’s ability to hide and replicate. This approach could be a major advance in the fight against HIV by making treatments more effective.

“What the research is trying to figure out is what we can do to get more of the drugs used to fight HIV into these cells that the virus can infect,” Dr. Cory said. “Infection in macrophages looks different; some of the drugs may or may not have similar efficacy as they would in CD4, and the cells themselves function differently.”

A dynamic and evolving field, other research teams across the country are investigating how macrophages behave, particularly regarding drug delivery to these immune cells. According to Dr. Cory, his approach differs significantly because it emphasizes the diverse roles of macrophages throughout their activity spectrum, rather than viewing macrophages as a single, uniform cell type, as is often done. This distinction is crucial because macrophages can adopt various functions, from pro-inflammatory to anti-inflammatory and reparative states.

Dr. Cory’s research will focus on two main objectives. First, he and his team will examine existing ART drugs to see how drug concentrations vary inside macrophages for each medication. He hopes to identify which drugs penetrate better, which have less penetration, and what that means for viral replication inside macrophages. Once this data is collected, he plans to conduct tests to find ways to increase drug delivery into these cells – for example, whether blocking a specific protein or targeting a certain cellular signal could enhance drug penetration into these hard-to-reach infected cells.

By focusing on enhancing drug delivery to these hidden reservoirs within the body, Dr. Cory hopes his research will lead to more effective therapies and ultimately bring us closer to the goal of complete viral eradication. Although the journey is long and complex, the support provided by the NIH grant will be instrumental in advancing this important research, paving the way for future breakthroughs in HIV treatment.