Take-home message: no AIDS magic bullet.

Almost daily, in venues as varied as chemistry journals and gene-therapy conferences, scientists report progress in the race to understand and quell AIDS, Sometimes. the media and researchers champion advances as leaps forward. Other times, they take a more conservative view, calling results tiny steps no more deserving of headlines and air time than any other research finding.

Fortunately, science eventually provides the perspective to put these advances in their proper places. Unfortunately, that perspective all too often reminds AIDS researchers that HIV, the virus responsible for this disease, can outmaneuver efforts to control it.

Such was the case with an unusual anti-AIDS strategy proposed last Februan) Researchers studying the effects of various drug combinations on HIV replication in cells grown in the laboratory discovered that sometimes, as the virus evolves resistance to these drugs, it also becomes less able to survive.

To deflect the toxic effects of anti-AIDS medications such as zidovudine (AZT) or dideoxyinosine (ddI), HIV mutates. Each mutation causes a change in a key HIV enzyme, reverse transcriptase. When bombarded with AZT, ddI, and another anti-AIDS compound called pyridinone, mutations change the enzyme so much that the virus cannot replicate, Yung-Kang Chow and his colleagues at Massachusetts General Hospital in Boston reported in the Feb. 18 NATURE. They tested this concept by creating mutant HIV that contained the four genetic changes known to lead to resistance to these drugs. As suspected, the virus could not infect cells.

But the triple whammy doesn't always work, British AIDS researchers now report. Sometimes, viable HIV that is resistant to multiple drugs does evolve, says Brendan A. Larder of Wellcome Research Laboratories in Beckenham, England. In the Sept. 30 NATURE, he and his colleagues describe experiments in which they subjected HIV that was already resistant to AZT and ddI to another drug, nevirapine. Later, they exposed the virus to all three drugs. In one case, HIV with the same mutations as the virus created by the Boston group remained viable, in contrast to the Boston results.

In August, another research team, headed by Emilio A. Emini of Merck Research Laboratories in West Point, Pa., also reported that this same mutant HIV could still replicate. A reexamination of the genetic makeup of the Boston mutant revealed that the virus actually had a fifth, previously unnoticed mutation, says Martin S. Hirsch at Massachusetts General Hospital.

It seems. therefore, that a three-drug attack does not necessarily lead to a less functional enzyme - and thus to a disabled virus. However, treatment with combinations of medications may still prove useful because of the individual effects of each drug, notes Douglas D. Richman at the University of California, San Diego. Clinical trials now under way should reveal whether this strategy stems HIV infection in people, Hirsch notes.