Trials for Drug That Leaves HIV Defenseless

Recent in vitro experiments of the drug PA-457 potentially indicate a new class of HIV maturation inhibitor drugs that could be used to overcome HIV that is resistant to current treatments.

According to Graham Allaway of Gaithersburg, Md.-based Panacos Pharmaceuticals, which is developing PA-457, up to 80 percent of HIV patients on treatment show resistance to one or more of their drugs.

In the latest research, PA-457 disrupted the formation of HIV's capsid protein, the conical shield which stores and protects the RNA essential to HIV's replication. The drug binds to the capsid protein at a critical juncture when normally it is clipped apart from the structural gag protein and assembled into a cone. PA-457 stops the capsid from being clipped, causing the sphere to be permeable, leaving the RNA exposed and HIV unable to infect human cells.

Previous lab experiments have shown resistant viruses succumb, unable to infect human cells. A small human trial reported last August showed PA-457 reduced HIV by tenfold in the blood within hours. Later this month, PA-457 will be combined with other HIV drugs and tested in a placebo-controlled trial among 48 patients whose existing treatments are failing.

The full report on the research, "3-O-(3',3'-Dimethysuccinyl) Betulinic Acid Inhibits Maturation of the Human Immunodeficiency Virus Type 1 Gag Precursor Assembled In Vitro," was published in the Journal of Virology (2006;80(12):5716-5722).

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