Cracks are widening in the frontline defense against the AIDS virus--drugs that inhibit essential viral enzymes called proteases and reverse transcriptases. At the 12th World AIDS conference in Geneva, Switzerland, separate teams of U.S. and Swiss researchers reported today the first confirmed cases in which HIV strains resistant to both classes of drugs had been transmitted to new victims. While multidrug resistance does not come as a complete surprise, researchers had hoped that HIV, by mutating to survive exposure to both classes of compounds, would have rendered itself incapable of infecting new hosts.
HIV's ability to mutate rapidly--and, of course, to hide out in its host's immune system--has made AIDS one of the world's worst infectious disease epidemics. But the tide began to turn in late 1995 and early 1996, when the U.S. Food and Drug Administration approved the first 3 protease inhibitors, which prevent HIV's machinery from clipping newly formed viral proteins to just the right size needed to assemble a new virus. Used in combination with reverse transcriptase inhibitors, which prevent HIV's genome from being incorporated in infected cells, the drugs caused new AIDS cases in the U.S. to decline 15% from early 1996 through mid-1997--the first decline since the epidemic began in 1981.
The drugs seemed just as promising as agents for blocking HIV transmission. Although AIDS patients regularly develop HIV strains resistant to one or more protease inhibitors, only a smattering of unconfirmed reports have suggested that the resistant strains--presumably less virulent because of mutations that help them survive drug treatment--could be passed to new victims. "The thinking had been that protease inhibitor-resistant virus was unlikely to be transmitted to new hosts," says epidemiologist Frederick Hecht of the University of California, San Francisco. At the conference, however, Hecht described a patient who had become infected with an HIV strain already resistant to six of the 11 approved antiretroviral drugs, including four protease inhibitors. A second study presented by researchers at the University Hospital of Geneva included three similar cases of drug-resistant HIV transmission.
These reports represent "the best documentation so far of multiple drug resistance in HIV," says infectious disease specialist Joel Gallant, director of the Moore HIV Clinic at the Johns Hopkins University School of Medicine. "We don't yet know the public health implications of multiple drug resistance, but it will probably become increasingly significant," Gallant observes, adding that it's a threat that underscores the need to prevent HIV transmission. Hecht concurs: "While we need to continue to develop new drugs to fight HIV, they're all likely to be plagued by resistance."