AZT falls short for kids with HIV.

Preliminary -- and unexpected -- results of a new study raise questions about using AZT, a standard anti-AIDS drug, to treat children with the disease.

In 1990, the Food and Drug Administration approved AZT (zidovudine) for use in youngsters who exhibit symptoms of infection with HIV, the virus leading to AIDS. Yet a government-sponsored clinical trial now indicates that the drug fails to halt the progression of HIV infection in children.

Investigators at 62 medical centers across the country recruited 839 children between the ages of 3 months and 18 years who had experienced symptoms of HIV infection. They gave one-third of the children AZT in the form of a strawberry-flavored syrup provided by the Burroughs Wellcome Co. in Research Triangle Park, N.C. Another third took a different antiviral drug called didanosine (ddI) from Bristol-Myers Squibb Co. in Princeton, N.J. The remainder received both AZT and ddI.

Neither the investigators nor the children and their parents knew which group was getting which of the three regimens. Furthermore, the children had received little or no treatment with anti-AIDS drugs in the past.

The National Institutes of Health in Bethesda, Md., which sponsored the study, assigned an independent board of scientists to check on the trial's progress. That panel's review of the interim data revealed that the group receiving only AZT fared much worse than the other two groups. On Feb. 8, NIH halted the AZT-only arm of the study. Kids who had been getting AZT alone were offered the option of switching to one of the other ongoing treatments.

"[The AZT portion of the] study was stopped over 6 months early because of the results," says study cochair Janet Englund of Baylor College of Medicine in Houston. "The finding that AZT was the least effective among the three options was quite a startling surprise," adds team member Ross E. McKinney Jr. of Duke University School of Medicine in Durham, N.C.

The data revealed that AIDS progressed more rapidly in youngsters getting just AZT, compared to children receiving ddI or the combination therapy. Children on AZT alone faced a higher risk of failure to grow, cognitive problems, the development of new opportunistic infections, and death.

In addition, kids getting the solo AZT treatment developed more side effects, such as low white blood cell counts, which can leave people with AIDS prey to infections.

"In the long run, AZT is not the best of the three choices [for children]," says James F. Balsley, chief of the pediatric medicine branch of NIH's National Institute of Allergy and Infectious Diseases. AZT remains a recommended drug treatment for adults with HIV infection.

Researchers don't know why kids on AZT alone fared so poorly. McKinney speculates that the children simply developed resistance to this drug. On average, kids in this study took AZT for 2 years, enough time for resistance to surface, Balsley notes.

NIH will not be able to tell physicians whether ddI or the combination approach is better until all the data in the ongoing trial have been collected and analyzed, a process that could take until the end of the year. However, many researchers believe that a combination of chemical weapons will ultimately prove most effective against this wily virus.