AIDS Drug's Safety in Spotlight

A controversial new study has put a cloud over one of the most stunning successes in AIDS. The anti-HIV drug AZT, when given to pregnant women infected with HIV, can reduce the likelihood of mother-to-child transmission by nearly 70%. But a study in pregnant mice now suggests that, at very high doses, the drug can cause tumors in offspring. The drug's manufacturer, however, has data suggesting that AZT at prescribed doses is safe. To get to the bottom of things, the National Institutes of Health has convened a blue-ribbon panel in Washington, D.C., that plans to issue a recommendation tomorrow morning.

The disturbing new study, headed by Lucy Anderson of the National Cancer Institute, shows that pregnant mice given megadoses of AZT gave birth to pups that were more likely to develop tumors of the liver, lungs, and genitourinary tract. Anderson's team found that AZT--which stops the AIDS virus from copying itself by interfering with viral DNA synthesis--had been incorporated into the pups' DNA in a variety of tissues, which they speculate may have led to the tumors.

At lower doses, however, there's no evidence of cancer risk. When researchers at Glaxo Wellcome, which makes AZT, gave pregnant mice doses similar to those given to people, they found no increased tumor risk in offspring. Nor have scientists seen evidence that children of AZT-treated mothers have higher tumor rates. Moreover, says Jack Killen, head of the AIDS division at the National Institute of Allergy and Infectious Diseases, researchers have known since 1989 that AZT can cause cancer in mice and yet haven't seen an increase in tumors in adults on the drug.

The panel meeting today has heard presentations from Anderson and the Glaxo Wellcome researchers and is now deliberating on the data. In principle, the panel could advise the Department of Health and Human Services to rescind its current recommendation that pregnant, HIV-infected women take AZT to prevent transmission to newborns. But that's unlikely to happen. "A lot of people have looked at this--ethicists, clinicians, basic researchers--and everyone agrees there's no basis for changing the recommendation," says Killen, the panel's chair. Still, he says, "we need to monitor the children carefully and carefully provide information to the public so that women facing the decision have it."