Carolina Researchers Discover Potential HIV Breakthrough Drug

UNC researchers discover way to make HIV cells visible to the immune system

January 31, 2020 

How HIV works

Those purple sponge like things in the picture above are HIV viruses. And since it was first identified in 1981, HIV (human immunodeficiency virus) remains one of humanity’s deadliest epidemics. It’s estimated 38 million people are infected with HVI worldwide with about 1.1 million patients in the United States. HIV is a virus that attacks the immune system, specifically the CD4 cells, or T-cells. Those cells are called “helper” cells because they don’t actually kill infection. They trigger the body’s response to infections.

During infection, HIV attaches to CD4 T-cells and unloads its genetic code into the cell to produce the HIV virions. The CD4 cells are killed in the process/ Over time, HIV destroys so many of those cells that the body can’t fight off infections and diseases. If left untreated, HIV can lead to the disease AIDS (acquired immunodeficiency syndrome). HIV is spread by contact with certain bodily fluids of a person with HIV, most commonly during unprotected sex or sharing needles for intravenous drug use. The human body can’t get rid of HIV and no effective HIV cure exists. So, once you have HIV, you have it for life.

Exposing HIV-infected cells

However, by taking HIV medicine (called antiretroviral therapy or ART), people with HIV can live long and healthy lives and prevent transmitting HIV to their sexual partners. And that’s where a discovery by scientists at the University of North Carolina at Chapel Hill and Emory University could make a lifesaving difference. Right now, antiretroviral therapy can suppress HIV to undetectable levels in the blood. However, the virus stays in the body, in latently infected CD4+ T cells. Because the virus is essentially hidden, the immune system can’t recognize the cells and there are no therapies to destroy them. But if ART therapy is stopped, the viral load explodes. That’s why HIV patients must stay on ART therapy.

The researchers discovered a compound called AZD5582 to expose latent HIV infected CD4+ T cells to attack. That’s been a challenge for years. How do you coax HIV out of latency, so it becomes visible to the immune system and allow an antiviral medication, or the body’s own immune response, to kill the virus-infected cells?

“No one had successfully tested a latency reversal molecule in animals with human cells that showed a reduction in HIV in peripheral blood or in resting CD4 T-cells,” said J Victor Garcia, PhD, professor of medicine, microbiology and immunology at the UNC School of Medicine. “We hope this will be an important step in eradicating the virus in people living with HIV.”

The study was done at the UNC School of Medicine using mice and also macaques. While it’s not clear if the strategy could be translated into human, the results open a new way to understand how HIV is controlled and how its expression can be manipulated. A lot more work is needed before testing could start in humans, but the discovery is considered a significant step forward towards developing an additional therapy. The study was published in Nature.

—Frank Graff 

 Frank Graff is a producer/reporter with UNC-TV, focusing on Sci NC, a broadcast and online science series.