Second Chances

For HIV-positive people who have developed resistance to available antiretroviral medications, the pipeline of new anti-HIV drugs is something of a mixed blessing. Although there are more than two dozen new drugs in clinical trials and scores of others in preclinical development, few are expected to hit the market within the next year. 'The most promising new drugs are taking quite a while to go through development,' Lei Chou, director of the Access Project at the AIDS Treatment Data Network, says. Only two new anti-HIV drugs are in final Phase III human trials'the nonnucleoside analog capravirine and the protease inhibitor tipranavir, which is a nonpeptidic drug that has a different chemical structure and resistance profile from existing protease drugs. Other candidates are at least two years away from Food and Drug Administration approval. Among the drugs in Phase II human studies that show significant activity against drug-resistant virus are two new nucleoside reverse transcriptase inhibitors'alovudine and elvucitabine'and two nonnucleoside drugs'calanolide A and TMC-125. Another protease inhibitor effective against drug-resistant virus'TMC-114'has progressed beyond initial safety trials. But among the most exciting medications in development that appear to be active against drug-resistant HIV are fusion inhibitors, which include drugs to prevent HIV's attachment, fusion, and entry into immune system cells, according to Warner Greene, MD, Ph.D., director of the Gladstone Institute for Virology and Immunology. Among the most advanced candidates in development is the attachment inhibitor PRO-542, currently in Phase II studies; at least a dozen more are in preclinical or early human tests. Some antibody-based entry inhibitors could be so powerful that they would need to be dosed only once a week'or even less often, researchers say. 'I'm basically optimistic that we'll continue to move in a direction where there are more and more choices and providers will really be able to tailor a drug combination to meet the needs of individual patients,' says Judith Feinberg, MD, an HIV specialist and the president of the Great Lakes chapter of the American Academy of HIV Medicine, 'because there's never a one-size-fits-all approach to this disease.'