As the world continues to fight the HIV epidemic, researchers across the globe are seeking groundbreaking solutions to improve treatment and patient care.

Among them is Sunday Ogundepo, currently pursuing his PhD at the University of Nebraska Medical Center (UNMC) in the United States.

Ogundepo, admitted into the institution in 2023 as a graduate assistant through the Interdisciplinary Graduate Program in Biomedical Sciences (IGPBS), is part of a research team focused on revolutionizing antiretroviral therapies (ART).

His work centers on the design, development, and evaluation of antiretroviral prodrugs, with a particular emphasis on long-acting slow effective release ART (LASER ART).

Prodrugs are formulations of medications that remain inactive when administered but become active once they interact with chemicals in the body. This innovative approach has significant implications for ART, particularly for HIV patients.

Prodrugs, such as those Ogundepo and his team are developing, are injected into the body, where they remain inactive in muscle tissues before slowly releasing active compounds.

This approach ensures a steady and controlled drug release over extended periods, vastly reducing the need for daily medication—a burden many HIV patients face.

“The concept of a prodrug,” Ogundepo explains, “is to create a formulation that doesn’t just work when you take it but activates when your body needs it, and that can change how we manage HIV treatment.”

A major focus of Ogundepo’s research is the development of LASER ART, a groundbreaking technique that could allow people living with HIV to reduce their medication to once every six months or even once a year. This would be a major improvement over the current regimen of daily pills, which many patients find challenging to maintain.

His team, led by Drs Howard Gendelman and Benson Edagwa, first introduced LASER ART to the world in November 2017. LASER ART works by unlocking storage areas in body cells where the drugs can reside for extended periods, helping to suppress the virus over time.

“Laser ART has the potential to reach tissue sanctuaries in the body that have remained hidden from conventional drugs,” Ogundepo notes.

These tissue sanctuaries, where HIV can persist, have been a significant obstacle in achieving complete viral suppression. Ogundepo and his team are optimistic that LASER ART will significantly improve the effectiveness of antiretroviral therapies and enhance patient adherence to treatment regimens.

The success of this research is already being recognized internationally. The team’s findings have been published in high-impact journals, including Nature Communications. Their article, titled “Transformation of dolutegravir into an ultra-long-acting parenteral prodrug formulation,” detailed successful studies in both rats and monkeys.

The article described how ultra-long-acting dosing intervals were well-tolerated by the animals, with some plasma drug levels detectable for up to a year following a single injection. “All our attempts to reproduce these results have been successful,” Ogundepo emphasizes, “which gives us confidence in the clinical potential of this formulation.”

Ogundepo’s research team is also working on bringing their invention to the market. They have partnered with industry stakeholders, including Exavir Therapeutics—a company co-founded by Prof. Edagwa, Dr. Howard Gendelman, and Alborz Yazi.
Exavir Therapeutics is dedicated to developing long-acting therapies for HIV, and their work on the prodrug formulation has recently garnered a $3 million award from the National Institutes of Health (NIH) and the National Institute of Allergy and Infectious Diseases (NIAID) to further advance the ultra-long-acting integrase inhibitor, XVIR-110.

This funding is a major step forward for the team as they move toward human clinical trials. While the process to license a new drug can take up to 10-15 years, Ogundepo believes that the timeline could be significantly shorter for their prodrug formulation. “We’re working with an existing drug that’s already been approved by regulatory bodies. Our job is to enhance its delivery and effectiveness, which should streamline the approval process,” he says optimistically.

Currently, the only licensed long-acting ART is Cabenuva, which consists of an injectable form of cabotegravir plus rilpivirine and requires patients to receive an injection once every two months. Ogundepo’s team is aiming for something even more groundbreaking: a treatment that can extend intervals between doses to as much as six months or a year.

Looking to the future, Ogundepo is hopeful that LASER ART will become a game-changer for both treatment and prevention of HIV.

“We believe that our work will make it possible for HIV patients to live more comfortably without the constant reminder of their illness through daily medication. This could really improve both adherence to treatment and overall quality of life,” he says.

The implications of this research extend beyond just treating HIV. LASER ART could also be used to deliver pre-exposure prophylaxis (PrEP) drugs that prevent HIV infection. This would be particularly beneficial for at-risk populations who struggle with adhering to the daily pill regimen currently required by PrEP therapies.

While there is still a long road ahead, Ogundepo’s research stands at the cutting edge of a new era in HIV treatment. His dedication to improving the lives of patients reflects his passion for scientific innovation and his commitment to finding practical solutions in the fight against HIV.

“We are not just aiming to create a better drug,” Ogundepo concludes. “We want to change how people live with this disease.”