A very small proportion of people living with the AIDS virus (HIV) are able to control it without the need for antiretroviral treatment. Researchers are providing insight into how this happens in these elite controllers, offering clues in the search for a cure.
Less than 0.5% of people infected with HIV can maintain such control of the virus without treatment. This is despite the presence of cellular reservoirs where dormant HIV is hiding.
To explain this phenomenon, the researchers compared the viral genomes that were integrated into the DNA of cells from 64 people with these untreated controllers with those of 41 patients on antiretroviral treatment.
The virus, in order to reproduce, needs to divert the program (genome) from the cells it infects and can lurk in dormant form, constituting viral reservoirs.
But according to work published in the scientific journal Nature, in these natural controllers, the virus has frequently integrated itself into places in the cell genome from which it cannot initiate its reproduction.
In most HIV-positive patients who do not have natural controllers, an effective lifelong treatment makes it possible to control the proliferation of HIV, without eradicating, a priori, the hidden viral reservoirs.
If treatment is stopped, full copies of the virus (called intact viral genomes) can proliferate and cause the disease to return.
In the very few people who control the virus without treatment, these reservoirs of the virus look different. Researchers have found fewer copies of the virus genome in them, but a higher proportion of the intact form that can proliferate.
What seems important is not the presence of intact viral genomes, but their location, according to Professor Xu Yu of Harvard Medical School, who led the research.
We found that in elite controllers, HIV was often found in places in the human genome that researchers call genetic deserts,” she told AFP.
In these inactive parts of the human genome, human DNA is never activated, so HIV remains in a blocked and locked state.
Professor Xu Yu
The authors suggest that this state of deep viral dormancy has a role in maintaining control without anti-HIV drugs, but is not completely permanent or irreversible.
The idea would be to target only intact viral genomes located in active parts of the human genome and ignore the others.
Moreover, in one elite controller, the researchers detected no intact HIV, despite analyzing more than 1.5 billion blood cells. This could mean that the patient is indeed cured, the team cautiously suggests.
2 HIV-positive persons, who had had a bone marrow transplant to treat cancer that apparently rid them of the virus known to be cured.
Last month, researchers reported the case of an HIV-positive Brazilian who, after receiving powerful antiviral treatment, spent more than a year without HIV treatment, remaining HIV-negative, without a bone marrow transplant.
Several prolonged remissions have also been reported around the world with no confirmed cure.