Novel Way to Trace HIV Mutations That Lead to Drug Resistance

A research team from UC San Diego and Harvard University has suggested a new approach to trace HIV mutations that lead to drug resistance.

They said once expanded to the full range of drugs available to treat the infection, it would allow doctors to tailor drug cocktails to the particular strains of the virus found in individual patients.

"We want to crack the code of resistance," said lead researcher Wei Wang, associate professor chemistry and biochemistry at UC San Diego.

To better understand which mutations matter for drug resistance, the researchers compared sequences of HIV taken from patients treated with specific drugs to those from untreated patients.

With the help of a novel statistical method, they identified clusters of mutations that seemed to be working together to help the virus escape treatment.

One drug, indinavir, targets a protein called protease, which the virus needs to assemble the capsule it uses to invade new cells.

Substitutions in ten different places on protease occurred in patients who were taking the drug, but what combination of mutations would hinder the action of the drug wasn't clear before this analysis.

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"People never looked at this, because they didn't know which mutation or which combination of mutations to study," Wang said.

"That's the advantage of using the statistical method first to find the patterns. After the statisticians discovered the connections between mutations, then we focused on those combinations. We built structural models to understand the molecular basis of drug resistance," Wang added.

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The study appears in Proceedings of the National Academy of Sciences.

Source-ANI
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