Potential New HIV Drugs Discovered Through Gene Variant Protection

A genetic variant found only in people of African ancestry may provide significant protection against HIV and offer insights for improved treatment strategies. This variant, unique to individuals with African ancestry, is thought to be present in up to 13% of this population. Those with this gene variant have viral loads that are 20 times lower compared to individuals with African ancestry but without the variant. Consequently, the former experience slower HIV progression and a reduced risk of transmitting the virus.

This genetic variant related to HIV is the first to be discovered in three decades and is particularly noteworthy as it is specific to people with genetic ties to Africa, where most of the world’s HIV cases are found. While advancements in treatment have reduced the spread of HIV, the virus readily mutates and evades drug effects.

Traditionally, genetic research on HIV has focused on individuals of European descent, leading to the identification of variants associated with reduced viral loads. These variants are found on the HLA and CCR5 genes, accounting for approximately 15% of the differences in HIV viral loads among people of European ancestry.

A recent study conducted by researchers at the National Microbiology Laboratory in Canada analyzed the DNA of 2682 men and women of African ancestry, most of whom were African Americans and tested positive for HIV-1. The study found that the participants’ viral loads were weakly associated with variants on the HLA gene, but not the CCR5 gene. However, the researchers also identified a relevant variant in a different gene called CHD1L, which is unique to people of African ancestry. This gene is located in a region of chromosome 1 known for encoding proteins involved in DNA repair.

To validate 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. The presence of this variant was found to be significantly associated with lower viral loads among those infected with HIV-1.

Further experiments were conducted by researchers at the University of Cambridge to elucidate how the variant affects HIV loads. They switched off the CHD1L variant in genetically modified human immune cells in the lab and exposed them to HIV-1. Interestingly, the virus replicated much more in macrophages, a type of immune cell, when the variant was switched off compared to when it was present. Surprisingly, this was not the case for another type of immune cell called T-cells, which are typically associated with HIV replication.

These findings have the potential to pave the way for more targeted management and treatment of HIV among people of African ancestry.