As the AIDS pandemic enters its third decade, viral resistance is beginning to counter the success of "highly active antiretroviral treatment" (HAART), the multidrug cocktails introduced in 1996. "Viral resistance is a significant problem, particularly for patients who began therapy in the pre-protease inhibitor era and who developed resistance to multiple reverse transcriptase inhibitors," says Robert Schooley, a professor of infectious diseases at the University of Colorado Health Sciences Center and national head of the AIDS Clinical Trials Group. The need for a new pharmaceutical strategy is more compelling than ever. Several novel and diverse drug candidates, however, are on the horizon.

According to the World Health Organization, at least 42 million people worldwide are HIV positive, and each day, 16,000 more become infected. Viral resistance, an inevitability of molecular evolution, arises when treatments do not totally suppress replication, so that variants can flourish. "HIV so far has been...

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