The National Institutes of Health (NIH) awarded a five-year, $29.15 million grant to the BEAT-HIV Martin Delaney Collaboratory in order to advance research initiatives working to find a cure for HIV. The goal of BEAT-HIV is to establish the most efficient method of combining different immunotherapies to ultimately eradicate HIV-1 in the human body.
BEAT-HIV is an amalgam of over 70 HIV researchers, helmed by principal investigator Luis J. Montaner, D.V.M., D. Phil., and Herbert Kean, M.D., chair of the HIV Research Program at The Wistar Institute Vaccine & Immunotherapy Center. The consortium is co-led by James L. Riley, Ph.D., microbiology professor at the University of Pennsylvania’s Perelman School of Medicine and Robert Siliciano, M.D., Ph.D., professor at the Johns Hopkins University School of Medicine. Community health organization Philadelphia FIGHT has been a part of the BEAT-HIV network for the last 25 years.
Scientists at Temple University’s Lewis Katz School of Medicine have also been carrying out cure-directed HIV research, and just received NIH grant money from the same program as BEAT-HIV to continue to do so. Principle investigators in the initiative are Katz School of Medicine faculty Kamel Khalili, Ph.D., professor and chair of the Department of Microbiology, Immunology and Inflammation as well as director of the Comprehensive NeuroAIDS Center; and Tricia H. Burdo, Ph.D., associate professor and associate chair of education in the Department of Microbiology, Immunology and Inflammation. The grant will fund their project “CRISPR for Cure,” which is based on the use of gene editing technology to find and destroy HIV in infected cells.
The grant money awarded to the research teams at the Wistar Institute and UPenn will be used for three main objectives: understanding the main mechanism behind the persistence of the viral reservoir (a group of HIV-infected immune cells not actively producing HIV) during antiretroviral therapy, which will help inform the second goal of attaining lasting suppression of HIV replication without antiretroviral therapy. The third goal of establishing new methods of annihilating the HIV reservoir will entail in part testing mRNA technology used in making of COVID-19 vaccines as a potential method of creating HIV-resistant cells.
“You can see how these three groups are interrelated,” Montaner said. “You have one measuring, one looking at control, and one looking at eradication. Whether the control leads to eradication or eradication leads to control without eradication, it’s up to the future — we don’t know.”
The goals build upon outcomes from two cure-directed clinical trials that the BEAT-HIV research teams have been conducting in Philadelphia. The trial that Montaner is spearheading involves the use of combination immunotherapies composed of two different broadly neutralizing antibodies and an interferon, or “an immune system modulator [that] actually activates the immune system,” Montaner explained.
“Mentally, [the interferon study] does wonders for you,” said William Carter, chairman of the BEAT-HIV Community Advisory Board (CAB) and a participant in both trials. “I have my own Walter Reed Center where I get checked out weekly, closely monitored. [Secondly,] I don’t have to wake up by 8:30 and have my pill in my system. I know it’s only one pill, but it just puts you on a whole different plane. I can truly be me, I don’t have to make sure I have my medicine with me – I know I’m fine.”
Dr. Riley and the team at UPenn are leading the other cure-directed trial, which centers on the use of gene therapy, in which scientists modify cells from a person living with HIV with instructions on how to find and kill the virus. The modified cells are then reinserted into the body.
The antibodies/interferon trial began in June, 2020 and includes 15 participants, while the gene therapy trial began in July, 2019 with 12 participants. Thus far, the trials have been met with unexpected success.
“We didn’t really plan for success in outcomes of control,” Montaner said. “Our trials are very detailed in every step of the way in introducing different immunotherapies, monitoring for potential complications, studying people after they stop immunotherapy for a period of three months and trying very carefully to follow their potential for viral rebound after they stop immunotherapy.”
The people who are toward the end of the trial who are being monitored are known as post-intervention controllers. “I think that they will be invaluable in telling us how to maintain control of the virus without any intervention,” Montaner said.
Carter, who is one of those post-intervention controllers, has gone one year without taking traditional HIV medication and approximately five months without any HIV medication at all, he said. “It’s been a blessing for me.”
Montaner has been keeping tabs on Carter’s progress on a weekly basis, collecting blood samples from him and documenting his history living with HIV.
“If last week there was some indication that the virus was coming out, let’s see what happens next week,” Montaner said. “We are literally watching the immune system of these individuals facing HIV. We need to wait for an opportunity when the material comes back to know, did the virus win or did the host win?”
If the virus is winning, the individual has to consider getting back on therapy. If the person is winning, then the scientists have more time to monitor how the virus is behaving and determine what needs to happen for the immune system to control the virus by itself, Montaner explained. “We have very unique outcomes happening in Philadelphia well beyond what’s expected.”
As co-chair of the BEAT-HIV CAB, Carter recruits community members to participate in the trials, facilitates conversation between participant and scientist and helps educate the community about the research happening via BEAT-HIV.
“I believe in the project,” Carter said. “I want to destroy myths of ‘us and them’ that all trials are bad because of things that happened in the past. I’m putting my money where my mouth is. It’s nice to have been invited to the table, but I’ve been invited into the kitchen to prepare the meal. I feel like I’m making history. I’m following in Tim Brown’s footsteps.”
Tim Brown was the first person to be cured of HIV via an experimental treatment for leukemia. He received a bone marrow transplant from a donor who had a rare mutation in part of their DNA that made them resistant to HIV. Brown died of leukemia in 2020.
Carter commented on the symbiotic relationship between the scientific teams that are leading the trials and the people participating in them.
“You need me as much as I need you,” Carter said, referring to the research teams. “I tell [the scientists,] ‘I need for you to continue to dream. Your dreams cause me to dream, so if you stop dreaming, I’m dead.’ I’m a healthy, 57-year-old man because of someone else’s dream.”
Philadelphia FIGHT has played a valuable role in the BEAT-HIV consortium by serving as a bridge between community members living with HIV and the clinical research initiatives.
“Active research participation by persons living with HIV is required for scientific advances and community voices help shape the science being done,” Philadelphia FIGHT Executive Director Jane Shull said in a press release. “The BEAT-HIV team includes this local, active and committed community working in partnership with the research team, which is central to its success.”
When asked what this research means for people living with HIV, Carter said, “It means that some people are learning how to live, some people are thriving. We’re teaching those who are learning how to live. It gives me hope. My granddaughter is 10. When she finishes college and then gets married, I get to see it.”