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Potential New HIV Drugs Discovered Through Gene Variant Protection

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

Nicholas Kajoba/Anadolu Agency/Getty Images

A gene variant found exclusively in individuals of African descent may provide significant protection against HIV. Understanding this variant could lead to improved treatments for HIV among these populations.

Approximately 13% of people of African ancestry possess this unique variant. Those with this gene variant and HIV have viral loads that are 20 times lower compared to individuals of African ancestry without the variant. This leads to a slower progression of HIV and a reduced risk of transmitting the virus, according to Harriet Groom at the University of Cambridge.

This discovery marks the first genetic variant related to HIV in three decades. Its significance lies in its specificity to people with African genetic ties, as the majority of global HIV cases are found in Africa. Despite advances in treatment, HIV easily mutates and evades the effects of drugs.

Previous genetic research on HIV mainly focused on individuals of European descent, which led to the identification of variants associated with reduced viral loads around 30 years ago. These variants are present in two genes known as HLA and CCR5 and contribute to about 15% of the variation in HIV viral loads among people of European ancestry.

Paul McLaren at the National Microbiology Laboratory in Canada and his colleagues conducted a study comparing the DNA of 2682 men and women of African ancestry, primarily African Americans, all of whom tested positive for HIV-1, the most common form of the virus.

The researchers found that the participants’ viral loads were somewhat linked to variants in the HLA gene, but not the CCR5 gene. However, unlike their European counterparts, a relevant variant was discovered in a different gene called CHD1L. This gene is located in a region of chromosome 1 known for encoding proteins involved in DNA repair. While all humans carry this gene, it is only found in people of African ancestry.

To confirm their findings, the researchers searched for the CHD1L variant in an additional 1197 people of African ancestry living with HIV-1 in multiple countries. They discovered that those individuals who possessed the variant – estimated to be between 4% and 13% of this population – had significantly lower viral loads when infected with HIV-1.

Seeking to understand how this variant affects HIV loads, Andrew Lever at the University of Cambridge and his colleagues, including Groom, disabled the variant in genetically modified human immune cells in the laboratory before exposing them to HIV-1.

After numerous trials, the team observed that the virus replicated more in macrophages, a type of immune cell, when the variant was turned off compared to when it was active. However, this was not the case for T-cells, another type of immune cell where HIV replication typically occurs, notes Groom. Further research may clarify the role of macrophages in HIV replication.

Cumulatively, these findings have the potential to facilitate more targeted management and treatment of HIV among individuals of African ancestry.

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