An international team of researchers has identified a genetic variant—the first new genetic variant related to HIV infection discovered in decades—that may explain why some people of African ancestry have naturally lower viral loads of HIV, reducing their risk of transmitting the virus and slowing progress of their own illness. The discovery could help direct the development of new treatment approaches for those living with HIV.

Researchers analyzed the genomes of almost 4,000 people of African ancestry living with HIV-1. In doing so, they identified a variant within a region on chromosome 1 containing the gene CHD1L which is associated with reduced viral load in carriers of the variant. Between four and 13 percent of people of African origin are thought to carry this variant.

This work is published in Nature in the paper, “Africa-specific human genetic variation near CHD1L associates with HIV-1 load.”

HIV remains a major threat to global health. According to UNAIDS, there were 38.4 million people living with HIV globally in 2021. And while treatments have improved dramatically since the virus was first identified, 650,000 people still died from AIDS-related illnesses in that year.

It is known that viral load varies widely among infected individuals, influenced by a number of factors including an individual’s genetic makeup. Most of the information regarding the relationship between genetics and HIV comes from studies among European populations. But certain aspects of infection, such as viral load, is known to vary widely among infected individuals, influenced by a number of factors including an individual’s genetic makeup.

Given that HIV disproportionately affects people on the African continent, it’s important to better understand the role of genetics in HIV infection in African populations.

“African populations are still drastically underrepresented in human DNA studies, despite experiencing the highest burden of HIV infection,” notes Paul McLaren, PhD, Public Health Agency of Canada’s National Microbiology Laboratory. “By studying a large sample of people of African ancestry, we’ve been able to identify a new genetic variant that only exists in this population and which is linked to lower HIV viral loads.”

The gene CHD1L is known to play a role in repairing damaged DNA, though it is not clear why the variant should be important in reducing viral load. Researchers used stem cells to generate variants of cells that HIV can infect in which CHD1L had either been switched off or its activity turned down. HIV replicated better in macrophages when CHD1L was switched off. Surprisingly, there was no effect in T cells—where most HIV replication occurs.

“This gene seems to be important to controlling viral load in people of African ancestry,” notes Harriett Groom, PhD, research fellow at Sidney Sussex College, University of Cambridge, U.K. “Although we don’t yet know how it’s doing this, every time we discover something new about HIV control, we learn something new about the virus and something new about the cell. The link between HIV replication in macrophages and viral load is particularly interesting and unexpected.”

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