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Naturally Resistant HIV Foils Therapy

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HIV's rapid mutation rates can lead to the evolution of drug resistance in HIV-positive patients receiving antiretroviral therapy, but naturally occurring resistance mutations can also accumulate to establish highly resistant HIV strains, according to new models published today (June 7) in PLoS Computational Biology. If true, the models suggest new interpretation for why HIV drug therapy can fail right off the bat.

"The paper is interesting, and may be important for getting scientists to think about evolution of drug resistance," said Andrew Read, an evolutionary biologist at Pennsylvania State University who did not participate in the study. "The mechanism of drug resistance seems straightforward, but it's not." Even relatively simple questions, like whether drug resistance can be avoided by cycling between two different drugs, randomly assigning the drugs, or giving all patients both, have yet to be answered, added Read, who studies the evolution of malaria drug resistance.

Scientists have been debating the relative contributions of pre-existing mutations and mutations that arise after therapy begins to HIV drug resistance since the mid-1990s, explained Robert Shafer, who studies mechanisms of evolved HIV drug resistance at Stanford University but was not involved in the project. It's generally understood that a multi-drug regimen works to prevent resistance from becoming established by forcing the HIV virus to acquire several mutations--raising the "genetic barrier" to resistance--and making it highly unlikely that viruses carry enough mutations before therapy, said Shafer.

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