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UNC researchers contribute to breakthrough in HIV cure research

UNC-Chapel Hill HIV researchers David Margolis, MD, and J. Victor Garcia, PhD, along with Rick Dunham from ViiV Healthcare (from left to right). Margolis is director of the UNC HIV Cure Center, which is home to Qura Therapeutics, a company formed through a partnership between UNC-Chapel Hill and ViiV, formerly the HIV research wing of GSK. Photographed January 21, 2020 at the Genetic Medicine Building on the campus of the University of North Carolina at Chapel Hill. Photo courtesy of Jon Gardiner/UNC-Chapel Hill.

A collaboration between UNC, Emory University and Qura Therapeutics has allowed for a breakthrough in HIV cure research.

The new research at UNC's HIV Cure Center involves a discovery that could reveal and reactivate latent cells, which when paired with clearance strategies have the potential to purge the HIV reservoir and achieve a cure. 

Latency refers to HIV’s ability to exist in a silent form once it integrates into the host cell genome, said Dr. Ann Chahroudi, associate professor of pediatrics at Emory and director of the Center for Childhood Infections and Vaccines at Emory and Children’s Healthcare of Atlanta. 

“We were able to reverse SIV latency in rhesus macaques and HIV latency in humanized mice and the mouse work was all done in Victor Garcia-Martinez’s lab at UNC,” Chahroudi said. 

Chahroudi said the team of researchers also tested on monkeys, finding similar results as the humanized mouse model. She said these consistent results confirmed the team's confidence in their ability to reverse latency cells.  

It is important to note that a pill to cure HIV is not simply around the corner, Dr. David Margolis, director of the UNC HIV Cure Center, said. 

Some of the challenges of the virus include how it integrates itself into the genetic material of human cells, Chahroudi said.

"In a way, it becomes a foreign gene that is living in the human cell," Margolis said. "That cell looks like any other cell in the body, so there is no drug or immune response that can see it. Once the sleeping virus is re-awoken, it spreads."

The long-lived persistence of the HIV virus in the body makes it difficult to eradicate, due to latently infected cells that escape the body’s immune system, according to UNC's HIV Cure Center. 

“When it is silent and integrated into the host cell genome, it is not visible to the immune system, and so the immune system basically doesn’t have a way to attack it when it’s in this latent form,” Chahroudi said. 

People who are infected with HIV and treated with standard antiviral treatment — which is effective at suppressing virus replication — are still at risk by HIV’s nature, Chahroudi said.

“In order to try to enable the immune system to now be able to see the virus in patients or monkeys or mice who are treated with AVT you need to test different approaches to try to reverse that latency,” Chahroudi said. “That basically means reawakening the virus, or activating the virus, in order to now express viral antigens that can be seen and targeting by the immune system.” 

The work on this project began in conjunction with the beginning of the UNC and ViiV Healthcare Limited partnership, said Richard Dunham, adjunct assistant professor in the UNC HIV Cure Center and director at ViiV Healthcare. 

“It’s really born at the interface of industry, academia, here at Qura," Dunham said. "We started on this work back in 2016/2017 and then worked our way from the lab to the mouse to the monkey over the last several years.”

Chahroudi said that despite the new research discoveries, no cure has been discovered. 

“Neither of them was able to reduce the level of what we call reservoirs, which is basically a persistent virus that's in cells,” Chahroudi said. 

Dunham said that about five years ago, UNC and ViiV Healthcare came to the realization that they could make more substantial progress toward curing HIV by working together. In the years that followed, the institutions created Qura Therapeutics and the UNC HIV Cure Center to conduct research. 

Emory University's HIV research team was added to further the partnership. 

“The overall principle here is that no one entity is really going to make that progress against HIV," Dunham said. "We feel like this partnership between industry and academia might help us to take these different and diverse approaches between the two types of organizations to work together to find an HIV cure." 

Chahroudi said the next steps for the research include combining both of the latency-reversing strategies discovered at UNC and Emory to boost the immune response against the affected cells.

“If we’re able to reawaken or reactive the virus and then treat the animals with different immune-boosting or aiding strategies, we hope that combination may have an impact on the level of virus reservoirs,” Chahroudi said. 

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The goal for researchers at UNC is to make the chemical that treats latent cells into a drug that can be used in people, Margolis said.