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March 6, 2008

Bevirimat Success Hinges on HIV Mutations

The experimental maturation inhibitor, Bevirimat (PA-457), is most effective in people whose virus does not carry a specific group of genetic mutations in HIV’s Gag protein, announced the drug’s developer, Panacos.

Bevirimat, which stops newly assembled viral particles from maturing into an effective and infectious state, is the first of a new class of drugs known as maturation inhibitors. It has been studied in a number of phase IIb studies at multiple doses and formulations. Depending on the dose and formulation used, participants in the studies have had varying virologic responses, ranging from no reduction in virus to a reduction of more than 1.46 logs.

Panacos evaluated the study participants’ virus and found that the participant’s virologic response depended heavily on whether or not the Gag protein of a participant’s virus had polymorphisms—multiple mutations in the protein’s structure. After sampling the virus of 100 patients in the company’s database, they found that roughly 50 percent did not have Gag polymorphisms, meaning that roughly 50 percent would likely respond to bevirimat.

Testing for the polymorphisms could be accomplished by updating the list of genetic changes already looked for with standard genotypic resistance tests. Panacos has not yet announced what dose or formulation of bevirimat may be used in future studies.

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