Genetics Determine Tolerance to HIV Infection

Study finds tolerance varies between individuals determined by their genes.

An individual’s genetics play a crucial role in determining their tolerance to HIV infection, according to the results of a recent study.

Published on September 16, 2014, in PLOS Biology, the study found that tolerance varies between individuals determined at least partly by inherited genes, which are unique from genes that influence resistance.

The researchers noted that immediately following the initial infection, HIV resides in a population of CD4+ T cells. A few months after infection, resistance can be measured by the set-point viral load, which indicates how well a person is fighting the virus.

The rate at which an infected person loses CD4+ T cells indicates how well they are tolerating the infection. When the number of CD4+ T cells falls below 200 cells per microliter of blood, the immune system is compromised as HIV becomes AIDS, which can lead to death if untreated.

The study examined more than 3000 HIV-infected patients from a Swiss cohort study to measure the set-point viral load and the rate of CD4+ T cell loss. The researchers used both values to evaluate resistance and tolerance, which were combined with demographic and genetic data to determine the workings of tolerance.

The researchers determined that men and women tolerate HIV equally, but age plays a more significant role in disease progression. The disease was found to progress nearly twice as rapidly in a patient 60 years of age than in a 20-year old.

More significantly, the study found that genetic characteristics associated with HIV resistance were not also associated with tolerance, which supported the notion that resistance and tolerance are biologically distinct phenomena. The study did find that the HLA-B gene, which is involved in resistance, also seems to play a role in tolerance.

The gene, which encodes a protein involved in recognizing pathogens by the immune system, varies considerably between individuals, according to the study. While some of the variants are known to influence HIV resistance, the researchers found other variants of the HLA-B gene also correlated with tolerance.

Tolerance and resistance were not found to be mutually exclusive, however, as they could be independent or go hand-in-hand, the researchers wrote.

The study authors noted that the work represents an important step in examining how tolerance works in humans, which may allow the process to be manipulated, thereby helping people to live more comfortably and for a longer duration with HIV.