“We have discovered a new genetic variant associated with the slow progression of HIV infection, after studying the genomes of almost 4,000 people who live with the virus and have African ancestors,” says Josep Maria Miró, one of the researchers on the study who has just published Nature, and a senior consultant at the Infectious Diseases Service at Clínic Barcelona and Idibaps.

This genetic characteristic “is more present in people who, despite not taking HIV treatment, have a low amount of virus in their blood,” says another of the scientists involved in the finding, Javier Martínez-Picado, an Icrea researcher at IrsiCaixa.

“Until now, in the previous studies carried out mainly with Caucasian people, this genetic modification had not been detected,” explains Javier Martínez-Picado, who indicates that the work has also confirmed the presence of a genetic variant on chromosome 6 previously found in the population. of European descent.

An infection that slows down in macrophages

The mutation, identified in the CHD1L gene present on chromosome 1, contributes to stopping the multiplication of the virus in cells. Specifically, in macrophages, key elements in the immune response and in maintaining the persistence of HIV infection.

The finding is due to a series of experiments with modified cells to express or not the gene. “When cells do not express it, HIV replicates with more difficulties; specifically, the most affected are macrophages, which are involved in activating the immune response and maintaining the viral reservoir”, explains Josep Maria Miró, Professor of Medicine at the University of Barcelona and researcher at CiberInfec.

According to UNAIDS 2021 data, some 38.4 million people are living with HIV worldwide.. Antiretroviral treatment manages to keep the infection at bay in the vast majority, although in 2021 650,000 people died of AIDS.

The viral load set point (in scientific jargon known by its English acronym, spVL) measures the concentration of HIV in the chronic stage of the infection, when the replication of the virus is more or less stable. The spVL varies among the infected population, depending on the ability of each immune system to control replication without antiretroviral drugs.

Factors such as the genetic profile of each individual influence this control, but most of the information in this regard comes from genomic analyzes of populations with European ancestors.

“Despite the high incidence of HIV infection in the African population, it is underrepresented in human genomics studies,” warns Javier Martínez-Picado. “Studies like this allow us to have a more representative genetic map of the global population.”

population variety

The results also show “the importance of carrying out genomic studies in populations of different ancestry to better address the specific medical needs of each person and avoid global health inequalities,” says the Irsicaixa scientist.

The research team, within the framework of the International Consortium for HIV Genomics, has accurately analyzed the genome of 3,879 people of African descent and HIV infection. The co-directors of the study are Jacques Fellay, from the Federal Polytechnic School of Lausanne (EPFL); Paul McLaren, of the Public Health Agency of Canada, and Manjinder Sandhu, of Imperial College, London.

In addition to better understanding the peculiarities of the patients, the finding, says Josep Maria Miró, “helps to characterize the genetic variables that allow better control of HIV infection. They are variables that can serve as therapeutic targets”, he suggests and, in this way, “have different flanks from which to attack HIV”.