Both Viral and Human Genetics Influence HIV Disease Progression

New research suggests that human and viral genetics account for one third of the differences in disease progression rates in HIV-positive individuals.

With a staggering 36.7 million individuals living with HIV around the world, researchers are dedicating their efforts into improving their understanding of the virus in order to better control it. One of the areas in need of further exploration is the progression of the disease, and how it differs from person-to-person.

To this end, new research published in PLOS Computational Biology has found that both human and viral genetics are responsible for one third of the differences in “disease progression rates” in HIV-positive individuals. The findings indicate that these genetics impact disease progression “by triggering mutations in the HIV viral genome,” according to a press release on the study.

If left untreated, HIV progresses in three main stages: acute infection, clinical latency or chronic HIV infection, and then, AIDS.

Researchers already know that the disease will progress at a faster rate in those individuals with higher viral loads, which, “refers to the amount of HIV in a sample of…blood.” The higher the viral load is, the more HIV is present in an infected individual’s body, which means that their immune system is not fighting off the virus as well.

Previous studies have found that when it comes to an infected individual’s viral load, there are two key influencers: an individual’s genetics and the genetics of their particular HIV strain. According to the study authors, “HIV is an extremely variable and adaptive organism with a rapid replication time, and high rates of mutation. Within-host evolution of the viral population occurs during the chronic phase of infection in which the pathogen adapts to its host environment.” Keeping this information in mind, István Bartha of École Polytechnique Fédérale de Lausanne, Switzerland, and colleagues are now the first scientists to further explore “the relative impacts of human and viral genetics on viral load within the same group of patients.”

In two prospective cohort studies, the scientists gathered both patient and genetic data from 541 HIV-positive individuals in Switzerland and Canada. Using linear mixed modeling, the scientists sought to find out how these genetics impact viral loads among HIV-positive patients.

Their findings? Genetic differences among HIV strains account for 29% of viral load differences among patients and “human genetic variation” account for 8.4% of differences. According to the press release, “Together, they explain just 30% of viral load variation, indicating that patient genetics exert most of its influence by inducing genetic mutations in the HIV virus as it multiplies inside the patient.”

When speaking of the implications of their findings, study director Jacques Fellay, PhD, explained, “Our paper demonstrates that the genetic make-up of both the patient and the infecting virus contribute to the clinical course of HIV infection.”

In order to “confirm and refine” the findings suggested in the study, a study consisting of a larger group of patients is needed. According to Dr. Fellay, “Combining host and pathogen data gave us new insight into the genetic determinants of HIV control.” Additionally, “A similar strategy could be used to better understand other chronic infectious diseases.”