Researchers from George Mason University’s Center for Infectious Disease Research (CIDR) and Tulane National Primate Research Center conducted a groundbreaking proof-of-concept study in Nature‘S Gene therapy who found an HIV-like virus particle that could eliminate the need for lifelong medications. Scientists have made great progress in treating HIV (human immunodeficiency virus) in recent decades, but people with the virus still need to take lifelong antiretroviral therapy (ART) because the disease is difficult to eradicate.
CIDR researchers, led by Yuntao Wu, professor at George Mason’s School of Systems Biology and principal investigator of the NIH-funded study, developed a special HIV-like virus particle, called HIV Rev-dependent lentiviral vector, that uses a HIV protein, Rev, as a trigger to selectively target and activate therapeutic genes in HIV-infected cells. The Mason team, consisting of Brian Hetrick, Mark Spear, Jia Guo, Huizhi Liang, Yajing Fu, Zhijun Yang and Ali Andalibi, has been developing the HIV Rev-dependent vector technology since 2002.
According to Wu, patients must take medications for the rest of their lives due to the persistence of HIV reservoirs, which are infected immune cells that harbor the virus. Currently, ART used by patients can effectively block the virus, but cannot eliminate viral reservoirs. Experimental approaches such as “shock and kill” and “block and lock” of the reservoirs are in development to eliminate or silence viral reservoirs. Wu said the HIV Rev-dependent lentiviral vector technology his team developed uses a different approach, which relies on the HIV Rev protein to selectively target reservoirs for killing or inactivation.
“Our approach shows signs of not only reducing viral reservoirs but also stimulating the immune system to produce antiviral neutralizing antibodies,” said Wu. “Think about turning a bad guy into a good guy.”
The reservoir cells can be targeted by the Rev-dependent vector and converted to release defective viruses that can act as a vaccine to stimulate neutralizing antibodies. Wu’s team called this new approach “rehabilitation and redemption” of the HIV reservoirs.
Scientists from the Tulane National Primate Research Center, including Summer Siddiqui, Lara Doyle-Meyers, Bapi Pahar, Ronald S. Veazey, Jason Dufour and Binhua Ling, worked with Wu’s team to test this technology on monkeys infected with SIVmac239 (a virus similar to HIV), in which one monkey found that virus levels in the blood and brain usually fell to undetectable levels for more than two years after discontinuation of ART.
According to Hetrick, this approach shows promise in controlling viremia and opens new avenues for developing effective treatments for HIV without relying on daily antiretrovirals.
“Our proof-of-concept animal studies demonstrate a step forward in the fight against this virus, bringing us closer to innovative and potentially transformative therapies for HIV patients,” said Hetrick.
This proof-of-concept study identifies what technologies could come to the 1.2 million people in the United States and 39 million people worldwide (as of 2022) with HIV who rely on medications to control the virus . Additional funded studies are needed to expand and optimize the animal studies, followed by human clinical trials as the next critical steps for developing the new treatment. Wu thanked the NYCDC AIDS Ride, organized by Marty Rosen, which raised money to keep his team going in its early years, leading to the more recent NIH-supported laboratory animals.
“It took us 20 years to take the first step, we will definitely continue,” Wu said.
