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Study hints at how 'elite controllers' stifle HIV

illustration of HIV and human DNA
(Image credit: Shutterstock)

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.

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"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.

Related: 11 surprising facts about the immune system  

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.

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. 

Nicoletta Lanese is a staff writer for Live Science covering health and medicine, along with an assortment of biology, animal, environment and climate stories. She holds degrees in neuroscience and dance from the University of Florida and a graduate certificate in science communication from the University of California, Santa Cruz. Her work has appeared in The Scientist Magazine, Science News, The San Jose Mercury News and Mongabay, among other outlets.

  • Chem721
    It seems that the "cure" for the disease in Willenberg's case is not a result of HIV's genome getting "trapped in genetic prisons", but is actually conferred by immune cells that kill off any and all cells which attempt to replicate it. A quote from the article:

    "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."

    end quote

    Such infected cells would be capable of some level of HIV replication, or present viral antigens on their surface, thereby exposing themselves to immune surveillance and elimination, at least in Willenberg's case.

    If so, the "cure" is not established by sequestering the genome in inaccessible areas, but rather by an active cellular immune response that destroys any attempt to make the virus by cells not "locked down". The presence of the HIV genome in "locked regions" after a "cure" is merely a default condition, and has no actual relationship to any "cure".

    Again, the "cure" it would seem is inferred by a unique immune response not seen in most people. In Willenberg's case, she had an effective subset of T-cells that allowed her to minimize viral replication by killing off any cells actively producing virus, or preparing to do so. "Locked out" HIV genomes are merely the end result of such a cure - with no HIV expression, there is no "reason" to kill those cells.

    Extended antiviral therapies might allow some people's cellular immunity to slowly develop an equivalent mechanism of killing all cells that try to make the virus, leaving only "locked out" cells as the only source of the viral genome. Those "locked out" cells may never be eliminated from the body since they never draw attention from immune surveillance because they never attempt to produce active virions.

    So it would seem that it is not the "lock out" of the HIV genome, but rather the elimination of all cells where it is not "locked out". Cells that sequester the genome spare themselves from certain death, and are not related to any "cure". Should any of these "locked out" cells change and begin to replicate the virus, they would be killed off by the T-cell response, the means by which a "cure" is actually established in people like Willenberg.

    As long as such T-cells remain active, the "cure" is likely too remain viable, assuming that complete viral elimination is never attained since there is evidence of a continuous low level virus production in most people who are infected regardless of immune competence, or for those who are on antiviral therapies.
  • Bob Roehr
    To read more of Loreen's story, try