How 'hidden mutations' fuel HIV drug resistance

Washington, Aug 1 : Researchers at McGill University have found how mutations hidden in previously ignored parts of the HIV genome play an important role in the development of drug resistance in AIDS patients.

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.

Gotte and his colleagues selected a few of these previously uncharacterised mutations and subjected them to a battery of highly sensitive biochemical tests.

"People were sceptical. The mechanism about how these mutations could be involved in resistance was not clear. However, in our paper, we present data that explains in considerable detail how these mutations work." Dr. Gotte said.

Nevertheless, he warned, the debate about whether to routinely screen these areas of the HIV genome will still likely continue for some time.

"It's extremely time-consuming and expensive to validate genotype testing. However, we probably will be testing these areas in a couple of years," he said.

Their study will be published on Aug. 8 in the Journal of Biological Chemistry.

ANI