Scientists believe that a mutation in a little-studied structural region of the AIDS virus may be behind resistance to several HIV drugs.
A report published in the open-access journal PLoS Medicine says that several mutations in reverse transcriptase (RT), the viral enzyme that copies the genes of HIV, are already known to cause drug resistance and are routinely detected in blood tests used by doctors to individualize HIV treatment.
The mutation that the scientist suspect to be the cause of HIV drug resistant is called N3481. The report suggests that this mutation is located not in the active part of RT, but rather in the so-called connection domain, which falls outside the region of the virus normally included in resistance tests.
During the study, the researchers analysed the first two-thirds of the RT gene in viruses isolated from more than 1,000 patients in Canada. They found that virus carrying the N348I mutation developed in more than 10 per cent of treatment-experienced patients.
It was observed that patients treated with the HIV drugs zidovudine and nevirapine were 2.6-times more likely to have the N348I mutation than others.
The report states that the mutation appeared early in therapy, often in viruses that had other resistance mutations. It further says that the appearance of the N348I mutation often coincided with an increase in the amount of HIV present in blood.
When the N348I mutation was introduced into HIV growing in the laboratory, the researchers found that it decreased the susceptibility of the virus to drugs, says the report.
Given that the N348I mutation confers resistance to two classes of RT inhibitor drugs and can emerge early during therapy, scientists are now believing that it may have a huge impact on patient responses to antiviral regimens that contain zidovudine and nevirapine.
The report stresses the need to determine whether looking for the N348I mutation may improve the ability of resistance tests to predict treatment outcomes.