Understanding HIV through Drug-Resistance

Acquired ImmunoDeficiency Syndrome (AIDS) is a disease that can result from chronic Human Immunodeficiency Virus (HIV) infection. Most commonly, HIV is transferred between individuals during unprotected sexual encounters and intravenous drug-use. HIV makes lots of mistakes when it copies its genome. Most of the time these mistakes (or ‘mutations’) are bad for the virus, preventing newly-made viral particles from infecting others. However, sometimes these mutations are advantageous, and allow the new viruses to evade recognition by human immune cells, or to resist antiviral drugs. Interestingly, when these viruses ‘evolve’ to resist antiviral drugs or prevent antibody binding, they also often become less ‘fit’, or less infectious than the original ‘parent’ virus. Thus, these adaptive mutations come with what is known as a ‘fitness cost’.

In this article, Swiss researchers used a combination of computers and DNA-sequencing technology to study HIV drug-resistance. In doing so, they were able to study how these mutations affect virus fitness. From blood samples collected from a large group of HIV-infected individuals (who agreed to be part of the study), the researchers determined which HIV mutations were found more frequently in each individual. These results gave them a good understanding of the populations of mutant HIV viruses in these individuals. Precise knowledge of these mutations may allow future researchers to make predictions about the relative ‘fitness’ of these viruses, and the relative risk posed to uninfected partners.

The goal of this research was to reduce the prevalence of highly-infectious drug-resistant viruses, while also determining which viruses are higher priority for new drug development. Ultimately, Kühnert et al. succeeded in this effort and were able to identify drug-resistant viruses of high interest in the HIV cohort they studied.

Summary written by: Landon Getz

To read the full article, please click the following link:

Quantifying the fitness cost of HIV-1 drug resistance mutations through phylodynamics

Denise Kühnert, Roger Kouyos, George Shirreff, Jūlija Pečerska, Alexandra U. Scherrer, Jürg Böni, Sabine Yerly, Thomas Klimkait, Vincent Aubert, Huldrych F. Günthard, Tanja Stadler, Sebastian Bonhoeffer, the Swiss HIV Cohort Study


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