The field of virology spends a substantial chunk of its resources inspecting every minute step of the HIV life cycle--from the binding and entry of the virus into an immune cell to its replication and release of a new virus from the host cell and, finally, the seeking of a new cell on which to prey. The last major new class of anti-HIV drugs emerged about a decade ago with the introduction of the protease inhibitors, which curb the action of an enzyme that is critical to a late stage of viral replication.
At the time, a few members of the HIV research community wondered whether protease inhibitors could provide the basis for a cure. The ingenuity of the virus has proved the hollowness of that hope. As many as half of HIV-positive patients under treatment in the U.S. were found in one study to be infected with viruses that have developed resistance to at least one of the drugs in their regimen. Clinicians can choose from more than 20 pharmaceuticals among protease inhibitors and two classes of drug that prevent the invading virus from copying its RNA into DNA, thereby sabotaging viral replication. Combinations of these agents are administered to counteract the virus's inherent mutability, but that strategy does not always ward off resistance to the medicines, including the protease inhibitors. "Given increasing resistance to protease inhibitors, it's of paramount importance to identify new ways to interfere with the virus replication cycle," asserts Eric Freed, a researcher in the HIV drug resistance program at the National Institutes of Health.