A handful of people with HIV can control the disease without treatment, and now research into these so-called elite controls provides clues in the search for a cure.
For most people with HIV, controlling the virus requires a daily, lifelong regimen of antiretroviral therapy (ART).
This treatment must be followed continuously because of the nature of HIV and how it replicates.
When it enters the body, HIV places copies of its viral genetic material inside the genome of a cell – and inserts itself effectively into the body’s code.
These viral reservoirs of HIV remain embedded even with ART and if a patient stops treatment, full-length copies of the virus – known as intact viral genomes – can spread, causing the disease to roar back and make them sick.
But in the very small number of HIV patients who can control the virus without ART, these so-called viral reservoirs of HIV do not seem to behave in the same way.
To learn more about why this is the case, a team of scientists tracked billions of cells from 64 elite controllers living with the virus without ART, and 41 people on ART.
They found fewer copies of the HIV genome in elite controllers, but a higher proportion of the copies were the genetically intact form that could probably spread.
– ‘Gene deserts’ –
But what appeared to be important was not the presence of intact viral genomes, but their location, said Xu Yu, a professor of medicine at Harvard Medical School, who led the study.
“We found that HIV in elite controllers was often found at locations of the human genome that researchers called ‘gene deserts,'” she told AFP.
“In these inactive parts of the human genome, human DNA is never turned on, and thus HIV … remains in a ‘blocked and locked’ state.”
The finding could change thinking about how to approach finding a cure for HIV, a disease with an estimated 38 million people living in 2019.
In the past it was assumed that if HIV were taken intact, a patient could still become ill.
But the sequence showed that even with intact, elite controllers remained healthy, as the virus moved further from areas called transcriptional launch sites, where the virus is more likely to become active and replicate.
The finding “gives us a blueprint of what a functional HIV drug looks like,” Yu said.
“We do not have to get rid of all the intact HIV sequences in their genomes – we only have to focus on those viruses that reside in active parts of the human genome.”
“The remaining sequences … do not appear to cause disease and it seems that they can be largely ignored.”
– Naturally cured HIV? –
The study also discovered an intriguing surprise: one elite controller appeared to have no intact HIV at all.
The researchers tracked 1.5 billion cells of the patient, would carefully search for hidden redoubts, but found none.
The team cautiously suggests that this may mean that the patient is healing themselves effectively.
Yu acknowledged that the suggestion was “provocative”, given the current concept of the virus.
It is believed that only two patients with HIV were cured of the virus after undergoing high-risk stem cell-bone marble transplants that were used to treat cancer but had the side effect of apparently freeing them from the virus.
Last month, investigators revealed another case involving an HIV-positive man who appeared to be effectively cured without the need for a bone marrow transplant.
After receiving several potent antiviral drugs, he was able to go without HIV treatment for more than a year and continued to test negative for HIV antibodies.
Yu said her team would now look for more elite controllers who have achieved a cure without treatment.
As found, these individuals can lead to a concept of HIV “as a disease that in rare cases can heal naturally”.
The team also plans to examine more ART patients in the longer term to see if anyone has similar virus profiles to elite controllers.
sah / jah / skonk
