More than ten years ago, Bruce Walker was working at Massachusetts General Hospital (MGH) when he was asked to see a patient who was claimed to be infected with the human immunodeficiency virus (HIV), but who was OK , despite the fact that he never took medication.
“Absolutely,” recalls Walker, an immunologist and doctor, “I did not really believe him.”
But it turned out to be true, and not just for this one patient.
Years of recent research have shown among 35 million people infected with HIV, there are a rare few who can suppress the virus themselves without treatment, and they are known as ‘elite controllers’.
Now, new research suggests that an even rarer subset may actually remove them from the virus without medical help.
Such a finding is remarkable because HIV is a lifelong condition without medical cure, and usually requires daily antiretroviral therapy (ART) to control the replication of the virus and stop developing acquired immune system (AIDS) from developing.
When HIV infects human cells, it copies its genetic material into the cell’s genome, creating a viral reservoir for replication.
Antiviral drugs can normally keep replication of these reservoirs at bay, at least up to a height. But there are others who do not need these medications at all.
Less than 0.5 percent of people infected with HIV seem to prevent the virus from replicating alone, and we are still not sure why or how.
“What happens to these individuals, whom we call elite controllers, can shed light on an HIV-1 cure and also help us understand how a person with HIV can control and prevent HIV-associated comorbidities , “says Keith Hoots, a director of blood disease research at the National Institutes of Health and a veteran HIV researcher himself.
In addition, a collaboration between MGH, MIT and Harvard has collected more than 1,500 confirmed cases of ‘elite control’. After years of digging, her research has revealed results previously known only through strict medical treatment.
While there are currently two cases where HIV is said to have been ‘cured’ by bone marrow transplants, the authors say that elite controllers are the closest thing we have to a possible “natural cure”.
Sequence of billions of cells from 64 HIV patients, who kept the virus at bay for a median of nine years without medication, and 41 people who took ART for a median of nine years, the team found something surprising.
Despite analyzing billions of their personal cells, one patient showed absolutely no intact HIV copies, and another patient had only one intact copy that was “warped and locked” in some sort of genomic targeted coat, which stops of replicating the virus.
This raises the possibility that a ‘sterilizing cure’ of HIV, in which the participant’s immune system has removed all intact HIV genomes from the body, can be achieved naturally in extremely rare cases.
In a Nature review of the paper, immunologist Nicolas Chomont says it will be difficult to show whether HIV in these two patients has been completely eradicated. That said, he admits, these cases are “very reminiscent of previous reports on HIV cures.”
Even elite controllers who had intact copies of the virus had them safely shut down.
Instead of being stored in active regions of the human genome, 45 percent of the viral reservoirs in elite controllers were discovered in ‘gene deserts’, where the patient’s DNA is still the genetic sequence introduced by the virus. , is effectively expressed, leading to sustained, drug-free ‘silencing’ of the virus.
People on ARTs, on the other hand, keep only 17 percent of their viral reservoirs in these inactive regions, which means that if they stop using their medications, most viral copies will begin to replicate again.
“This position of viral genomes in elite controllers,” says Yu, “is very atypical, as in the vast majority of people living with HIV-1, HIV lies in the active human genes where viruses can be easily produced. “
It is not clear what these differences are, but when the authors infected the cells of elite controllers with HIV, the virus integrated as usual into active genomic sites. So where did these copies go in the elite controllers?
Recent research suggests that T cells, which seek out and destroy infections, may play a role in clearing up the virus.
Far from HIV integrated at various genomic sites, the authors argue, it seems that elite controllers can eliminate proviral sequences on active transcription sites, carefully monitored by their immune system.
“In contrast, less transcriptionally active proviral sequences with features of deep latency, leading to lower vulnerability to immune recognition, appear to remain long-lasting,” they write.
This suggests that our immune system may have a way that researchers can use to target viral sequences at risk of replication. And while this does not change anything for HIV patients now, it does suggest a possible path to future treatment.
Rutologist Monica Roth of Rutgers University, who was not involved in the study, said Science News the idea that emerges in this newspaper is “intriguing” but that “there is no evidence that it happens” in reality.
Genomic research can only tell us so much that we need even more research to understand how the immune system of some people living with HIV can naturally suppress the virus.
The study was published in Nature.
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