Study hints at how ‘elite controllers’ stifle HIV

Some people with HIV have a seemingly miraculous ability to control the disease without life-long antiviral medications or risky bone marrow transplants, and now, a new study hints at how this “elite” group bridles the infection.

In less than 0.5% of people with HIV, the virus stops replicating without the need for drugs, even though some latent virus continues to persist in the body, according to the study, published Aug. 26 in the journal Nature. HIV hides out inside human genes, but the new research suggests that sometimes these genes tuck the pathogen away in regions of the genome where it cannot be copied, The New York Times reported, thus preventing the virus from replicating and keeping the infection under control. 

For one patient, the researchers were unable to detect any trace of the virus in blood cells, or in cells from her intestines or rectum, the Times reported. The 66-year-old patient, named Loreen Willenberg, has successfully suppressed the virus without medication for decades and has participated in studies of HIV for over 25 years. 

Although scientists have known about her case for years, data from the new study suggests she could perhaps be considered “cured” of the infection. To date, only two people in the world are considered cured of HIV, and both underwent bone-marrow transplants to make their immune systems resistant to the virus, Live Science previously reported. Willenberg would join the short list of fully-recovered HIV patients if she can be confirmed free of the virus.

“She could be added to the list of what I think is a cure, through a very different path” compared with bone-marrow transplantation, Dr. Sharon Lewin, director of the Peter Doherty Institute for Infection and Immunity, who was not involved in the study, told the Times. 

On the other hand, virologist Dr. Una O’Doherty of the University of Pennsylvania, who was not involved with the study, said she needs more data before confirming that Willenberg has been functionally cured of HIV. “It’s certainly encouraging, but speculative,” O’Doherty told the Times. 

The study authors speculated that some people taking antiviral drugs for HIV could potentially reach recovery as Willenberg might have, if the virus inside them gets similarly trapped in genetic prisons, unable to replicate. And in fact, about 10% of the people who control HIV with drugs can eventually stop taking antiviral medication and continue to suppress the virus without assistance, according to The New York Times; the new study hints at how that might be possible.

“It does suggest that treatment itself can cure people, which goes against all the dogma,” study author Dr. Steve Deeks, an AIDS expert at the University of California, San Francisco, told the Times.

In addition to Willenberg, the study included 63 other people who suppressed the virus without antiviral drugs, the Times reported. Among the 64 patients, 11 stood out as “exceptional controllers;” these individuals only had detectable levels of the virus in densely-packed regions of the genome where cells cannot readily access it. Normally, HIV would hijack the cellular machinery used to make proteins to instead make copies of itself, but when HIV genes get sequestered by certain genes, the pathogen has no way to replicate.

By analyzing the immune cells of study participants, the authors came up with a theory as to how the virus gets stuck in the first place. They suspect that, in some people, immune cells known as T-cells target and kill infected cells that carry HIV in easily-accessible portions of the genome — in regions where it can be copied. HIV remained untouched in cells where it was trapped in “blocked and locked” regions of the genome, senior author Dr. Xu Yu of the Ragon Institute told the Times.

“That’s really the only explanation” the researchers have for why the virus would persist in some cells without being able to replicate, study author Dr. Bruce Walker, a researcher at the Ragon Institute, told The New York Times.

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Since submitting the results of their study, the authors have found several other people like Willenberg who may be effectively cured of HIV, Yu told The New York Times. “We believe there’s definitely many of them out there,” he said. The team also aims to study people with HIV who have taken antivirals for decades, to see if their immune systems have similarly trapped the virus in genetic prisons.  

Still, it’s unclear if the findings could translate to most people with HIV. “The real challenge, of course, is how you can intervene to make this relevant to the 37 million people living with HIV,” Lewin told the Times. In other words, could these findings pave the way to a functional cure for others with the disease? We need more data to know for sure.

Originally published on Live Science. 

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