A man takes a tablet of medication
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One of the difficulties in finding a cure for HIV is the virus can lay dormant in hard-to-reach parts of the body.

An individual may have an undetectable load, and be unable to transmit it to others, but a small amount of dormant HIV remains hidden within the DNA of cells in the immune system. These so-called viral “reservoirs” can suddenly start to replicate HIV if treatment stops.

The recent International AIDS Society (IAS) Conference in Brisbane, Australia, heard from one researcher trying to tackle this problem.

Monica Reece is a Ph.D. candidate in the Microbiology and Genetics Program at Emory University in Atlanta. Georgia. She and colleagues have been testing out Jak (Janus kinase) inhibitors. They specifically looked at ruxolitinib. At her presentation, Reece said they found the medication leads to a significant decay in viral reservoirs.

Her colleague and senior study author, Dr. Christina Gavegnano, said in a statement, “The barrier to an HIV cure is that the virus hides inside the DNA of cells. The brass ring is an agent that can eliminate these reservoir cells, which would ultimately eliminate HIV from a person’s body.”

Gavegnano has been searching for this agent for several years. Jak inhibitors were discovered in 2010. Gavegnano and researcher Raymond Schinazi are listed on the issued patents as sole inventors.

Hidden HIV

The researchers did a study on people with a high reservoir viral load. The subjects were given ruxolitinib for five weeks in addition to their usual ART medication. The researchers looked specifically at levels of HIV hidden with DNA. They did a follow up seven weeks after the five week course of treatment and the results pointed to a dramatic decline in HIV.

Reece told Queerty, “We used the decay rate from the trial to make a prediction model for reservoir clearance which estimates 99.99% clearance in just under 3 years (2.86 yr).”

“These data suggest that our Jak inhibitors can not only reverse the immune dysfunction that prevents HIV-1 cure, but also significantly decay the reservoir in people living with HIV,” said Reece in a press statement.

“Collectively our trial demonstrates a mechanism by which ruxolitinib, or other Jak inhibitors such as baricitinib, also extensively studied by our group, decay the reservoir, which underscores potential for cure-based therapies.”

The team point out that, “the study focused on the peripheral viral reservoir and may not fully represent the entire viral reservoir within the body, including sanctuary sites where HIV can persist despite treatment.”

The Geneva patient

A couple of weeks ago, Queerty brought you news of a man who appeared cured of HIV following a stem cell transplant. Although this has happened before, this particular individual did not receive stem calls from someone with natural immunity to HIV. Researchers now want to know why the man—dubbed “the Geneva patient”—appears cured and what other factors may be at play. Interestingly, the individual concerned also took ruxolitinib.

“These data are valuable because they show that Jak inhibitors can contribute to a long-term cure strategy for HIV, but they can also be used to slow the inflammatory process caused by other infectious diseases,” says Vincent Marconi, MD, professor of medicine and global health at Emory University School of Medicine.

Marconi was involved in the trial reported above. He also says he’s looking at whether Jak inhibitors may be useful in treating long Covid.

The Emory team hopes further research into Jak inhibitors will reveal how they work, and if they can be tweaked to become an actual cure for HIV.

“The next step is to study Jak inhibitors in PWH [People with HIV] for a longer duration and with greater variety of samples,” Reece told Queerty. “This work only looked at the reservoir in the blood, but we need to know how the entire reservoir is affected, including the brain and gut.”

Matthew Hodson, Chief Executive of HIV information organization AIDSmap, told Queerty, “The persistence of a viral reservoir has confounded hopes for a cure for HIV for years. The high number of setbacks seen in cure research trials over the last few years means early positive signs from any novel treatment should be welcomed cautiously.”

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