How "hidden mutations" contribute to HIV drug resistance
黑料不打烊 researchers explain how previously ignored parts of HIV genome play key role
One of the major reasons that treatment for HIV/AIDS often doesn鈥檛 work as well as it should is resistance to the drugs involved. Now, scientists at 黑料不打烊 University have revealed how mutations hidden in previously ignored parts of the HIV genome play an important role in the development of drug resistance in AIDS patients. Their study will be published Aug. 8 in the Journal of Biological Chemistry.
鈥淗IV develops resistance very rapidly, and once that happens, drugs don鈥檛 work as well as they theoretically should, or they stop working altogether,鈥� explained Dr. Matthias G枚tte, an associate professor in 黑料不打烊鈥檚 Department of Microbiology and Immunology. 鈥淧hysicians routinely have the patient鈥檚 virus tested for resistance in advance of treatment to help make the appropriate clinical decisions.鈥�
The study was conducted by a team of researchers led by Dr. G枚tte at 黑料不打烊鈥檚 Faculty of Medicine, with assistance from the B.C. Centre for Excellence in HIV/AIDS at the University of British Columbia (UBC). It was funded by the Canadian Institutes for Health Research (CIHR).
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.
鈥淭he focus has been on specific areas of the HIV genome where we expect these resistance-conferring mutations to occur,鈥� Dr. G枚tte said. 鈥淲e 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.鈥�
Within the last few years, however, studies started to suggest that the first 300 amino acids alone may not completely describe the drug resistance landscape. Dr. G枚tte and his colleagues selected a few of these previously uncharacterized mutations and subjected them to a battery of highly sensitive biochemical tests.
鈥淧eople were skeptical,鈥� Dr. G枚tte said. 鈥淭he 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.鈥�
Nevertheless, he cautioned, the debate about whether to routinely screen these areas of the HIV genome will still likely continue for some time.
鈥淚t鈥檚 extremely time-consuming and expensive to validate genotype testing,鈥� he said. 鈥淗owever, we probably will be testing these areas in a couple of years.鈥�
