Thirty-five million people worldwide are affected by the Human Immunodeficiency Viruses, or HIV. There is no cure for the condition, but individuals can have a healthy and long life by taking antiretroviral therapy (ART) daily.
A very small fraction of individuals, less than 0.5 percent of people with HIV, can control the virus without ART. They are known as “elite controllers”. A new study published in Nature reports some important insights on just what makes these people special.
When HIV infects cells, its genetic material is incorporated in the genome of host cells, where it can replicate, creating many copies of the virus. These viral reservoirs are known as provirus. Now ART stops the virus from reproducing and being in circulation around the body, but it doesn’t affect these proviruses. If a person stops taking the medication, the provirus will once again start making new copies of HIV.
For this reason, scientists were interested in these elite controllers and how their cells can naturally suppress the virus. They compared billions of cells from 64 elite controllers against billions of cells against 41 individuals on ART.
They discovered that elite controllers had a lower number of proviruses in their cells compared to people taking ART, but those proviruses have more intact genetic material than in the people taking ART. Another important finding was the location in the genetic code of the viral reservoir. In elite controllers, it's in an inactive part of human DNA, so that is in a way locked in place.
"This positioning of viral genomes in elite controllers is highly atypical, as in the vast majority of people living with HIV-1, HIV is located in the active human genes where viruses can be readily produced," lead author Xu Yu, from the Ragon Institute of Massachusetts General Hospital, said in a statement.
Another surprising find was the discovery that one of the elite controller participants had no intact HIV in over 1.5 billion cells analyzed. This hints that a sterilizing cure of HIV could be possible naturally in extremely rare circumstances. The only other known case of this happened after a bone-marrow transplant.
The team wants to stress that the quality of being an elite controller is not completely permanent and irreversible. They hope that by understanding how these people’s cells eliminate active proviruses, it will go towards one day creating a functional cure for HIV.