Researchers from George Mason University’s Center for Infectious Disease Research (CIDR) and Tulane National Primate Research Center have made significant progress in finding a potential functional cure for HIV through a groundbreaking proof-of-concept study published in Nature‘s Gene Therapy. This study introduces an HIV-like virus particle that may eliminate the need for lifelong medications for individuals living with the virus.
Under the leadership of Yuntao Wu, a professor in George Mason’s School of Systems Biology and the principal investigator of the NIH-funded study, researchers at CIDR developed a unique HIV-like virus particle known as HIV Rev-dependent lentiviral vector. This particle leverages an HIV protein called Rev to selectively target and activate therapeutic genes in cells infected with HIV. Wu’s team, which includes Brian Hetrick, Mark Spear, Jia Guo, Huizhi Liang, Yajing Fu, Zhijun Yang, and Ali Andalibi, has been working on this technology since 2002.
Wu explained that current medications must be taken for life due to the presence of HIV reservoirs—infected immune cells housing the virus. While antiretroviral therapy (ART) effectively suppresses the virus, it does not eradicate these reservoirs. Various experimental methods like “shock and kill” and “block and lock” have been explored to eliminate or silence these reservoirs. In contrast, the HIV Rev-dependent lentiviral vector technology developed by Wu’s team operates differently by targeting reservoirs for deactivation or elimination through the Rev protein.
Wu stated, “Our approach not only reduces viral reservoirs but also enhances the immune system to produce antiviral neutralizing antibodies, essentially transforming a harmful element into a beneficial one.”
The Rev-dependent vector targets and transforms reservoir cells into releasing defective viruses, serving as a potential vaccine to trigger neutralizing antibodies. This innovative strategy is termed “rehab and redeem” for HIV reservoirs.
Collaborating with Wu’s team, scientists at Tulane National Primate Research Center examined this technology in monkeys infected with SIVmac239, a virus similar to HIV. Their findings revealed significant reductions in virus levels in the blood and brain of one monkey for over two years after discontinuing ART.
Hetrick noted that this approach shows promise in managing viremia and opens up new possibilities for developing effective HIV treatments that do not rely on daily antiretrovirals.
Hetrick expressed, “Our proof-of-concept animal studies represent progress in combating this virus, getting us closer to innovative and potentially transformative therapies for individuals living with HIV.”
This pioneering study indicates the future possibilities for the 1.2 million individuals in the United States and 39 million worldwide (as of 2022) living with HIV who rely on medications to control the virus. Additional funded research is crucial to expand and refine animal studies, paving the way for human clinical trials—an essential next phase in the development of this new treatment. Wu acknowledged the NYCDC AIDS Ride coordinated by Marty Rosen for the initial funding that supported his team in the early stages, leading to the recent NIH-funded animal trial.
Wu affirmed, “It took us two decades to take the first step, but we are determined to continue moving forward.”
