Gene variant that seems to protect against HIV may lead to new drugs


Someone having their blood tested for HIV in Kampala, Uganda, in December 2022

Someone having their blood tested for HIV in Kampala, Uganda, in December 2022

Nicholas Kajoba/Anadolu Agency/Getty Images

A genetic variant found only in people of African ancestry may offer them considerable protection against HIV. A better understanding of this could improve treatments for the infection among these populations.

Unique to people with African ancestry, up to 13 per cent of such people are thought to have this variant. Among people with HIV, the viral loads of those with this version of the gene are 20 times lower than those of people who are also of African ancestry, but lack the variant. As a result, the former have slower HIV progression and a reduced risk of transmitting the virus, says Harriet Groom at the University of Cambridge.

This is the first time a genetic variant related to HIV has been found in three decades, says Groom. It is also of particular significance since it is specific to people with genetic ties to Africa, where most of the world’s HIV cases are found, she says. Advances in treatment have reduced the spread of HIV since it was discovered, however, the virus easily mutates and evades the effects of drugs, says Groom.

Most genetic research on HIV has focused on people of European descent, which led to the discovery of variants associated with a reduced viral load about 30 years ago. Those variants, found on two genes known as HLA and CCR5, account for about 15 per cent of the differences in HIV viral loads among people of European ancestry.

Now, Paul McLaren at the National Microbiology Laboratory in Canada and his colleagues have compared the DNA of 2682 men and women of African ancestry, most of whom were African Americans. All were positive for HIV-1, the most common form of the virus.

The researchers found that the participants’ viral loads were somewhat associated with variants on the HLA gene, but not the CCR5 gene. However, unlike in people of European ancestry, they also found a relevant variant in a different gene, known as CHD1L. This gene is in a region of chromosome 1 that is known for encoding proteins involved in DNA repair, says Groom. All humans have this gene, but only people of African ancestry carry the newly discovered variant.

To confirm their findings, the researchers searched for the CHD1L variant in an additional 1197 people of African ancestry who were living with HIV-1 in multiple countries. They found that those who have the variant – an estimated 4 to 13 per cent of people of this ancestry – have significantly lower viral loads when infected with HIV-1, says Groom.

Wanting to understand how the variant affects HIV loads, Andrew Lever at the University of Cambridge and his colleagues, including Groom, experimentally switched it off in genetically modified human immune cells in the lab, before exposing them to HIV-1.

Over many trials, the team found that the virus replicated much more in one type of immune cell – macrophages – when the variant was switched off than when it wasn’t. Surprisingly, however, that wasn’t the case for another type of immune cell, T-cells, even though these are thought to be where most HIV replication usually occurs, says Groom. More research could shed light on the role of macrophages in HIV replication, she says.

Combined, the findings could, over time, lead to more-targeted management and treatment of HIV in people of African ancestry, says Groom.



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