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Overlooked Mutation Can Spur HIV Drug Resistance
Date:12/1/2007

onfer resistance to nevirapine and zidovudine and can augment resistance when in the presence of other drug mutations found in the N-terminal region of the enzyme."

The trouble is, standard genotyping tests are designed to pick up N-terminal mutations but they ignore the C-terminal region, including N3481.

According to Tachedjian, that means the finding "may have implications for genotypic resistance testing, particularly for patients on zidovudine and nevirapine therapy, and therefore should be considered for incorporation in [standard] genotyping assays."

The advent of new antiretroviral drugs means these gene tests are already going to have to be altered, she added, "and while we are making these changes it could be relatively straightforward to include" the C-terminal region, and N3481, in the tests as well.

Tachedjian believes other overlooked, resistance-conferring mutations might also be hiding out in the C-terminal region, and her team is currently looking into that possibility.

In the meantime, the N3481 discovery could have implications for AIDS drug development, Gotte pointed out.

"We learn a lot when we study mechanisms of resistance, in terms of what we should avoid in regard to drug development and how we can make drugs better," he said.

Gotte stressed that HIV-positive patients should not be overly concerned that their doctors are missing a key factor as they seek to determine the best treatment strategy.

While adding N3481 to the genotyping mix will improve treatment design, "it's still a minor piece of the puzzle that's missing here," he said. "I wouldn't be too worried about this because clinicians also look for other parameters" as they choose effective therapies, he added.

More information

Find out more about HIV at the U.S. National Institute of Allergy and Inf
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Overlooked Mutation Can Spur HIV Drug Resistance
Overlooked Mutation Can Spur HIV Drug Resistance
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