'Hidden Mutations' may Trigger HIV Drug Resistance

The mechanism behind how mutations hidden in previously ignored parts of the HIV genome play an important role in the development of drug resistance in AIDS patients, has been identifed by researchers at McGill University.

One of the major reasons that treatment for HIV/AIDS often doesn't work as well as it should is resistance to the drugs involved.

Now, McGill researchers explain how previously ignored parts of HIV genome contribute to HIV drug resistance.

"HIV develops resistance very rapidly, and once that happens, drugs don't work as well as they theoretically should, or they stop working altogether," explained Dr. Matthias Gotte, an associate professor in McGill's Department of Microbiology and Immunology.

"Physicians routinely have the patient's virus tested for resistance in advance of treatment to help make the appropriate clinical decisions," Gotte added.

HIV genotype testing is now widely established in HIV drug resistance screening. However, for technical and economic reasons, the entire HIV genome is usually not sequenced.

"The focus has been on specific areas of the HIV genome where we expect these resistance-conferring mutations to occur," Gotte said.

"We focus on a particular sequence on an important gene from amino acid 1 to 300, and as such, we miss roughly a third of this gene. Until recently, most researchers believed that this hidden area was of little clinical significance," Gotte added.

However, within the last few years, studies started to suggest that the first 300 amino acids alone might not completely describe the drug resistance landscape.