The study, published in Thursday's (June 12) issue of the New England Journal of Medicine, showed that a combination of didanosine and zidovudine, formerly called AZT, was superior to zidovudine alone in slowing progression of the illness and delaying death. It also revealed that didanosine alone worked even better than the combination because of fewer side effects.
"These somewhat surprising findings are new and important because until now, zidovudine has been the drug of choice for treating children who have AIDS-related symptoms," said Dr. Wilma Lim, clinical assistant professor of pediatrics at the University of North Carolina at Chapel Hill School of Medicine and a contributor to the study. "This large, long-term carefully done study shows zidovudine is not as good."
Lim treats children infected with HIV -- the AIDS virus -- every day.
Dr. Janet A. Englund of Baylor College of Medicine coordinated the study, which involved scores of researchers at 78 hospitals from North Carolina to California. In what is known as a randomized, double-blind clinical trial, researchers evaluated how 831 children did on either drug or on a combination of the two.
HIV-infected children, 90 percent of whom were infected at birth, were enrolled between August 1991 and August 1993. They were divided into two age groups -- below and above 30 months old -- and randomly assigned to one of the three treatment groups. Ninety-two percent had not received such antiretroviral therapy before. Such drugs are called nucleoside analogues.
"An analysis of how the children were doing after an average of 23 months showed a significantly higher risk of disease progression or death among patients receiving zidovudine alone than in those receiving the other two treatments," Lim said. "For that reason, that part of the study was stopped, and the research continued with the combination treatment or didanosine alone."
After nearly three years, analysis of results nationwide showed that children who received didanosine alone faced a lower risk of anemia or blood cell damage, she said. The study also showed children tolerate long-term antiretroviral therapy.
"Despite growing optimism that combination antiviral regimens, particularly those that include a protease inhibitor, can delay disease progression and prolong survival in HIV-infected adults, serious hurdles must be overcome before such therapy can be routinely applied to pediatric patients," Englund wrote.
"Important problems remain, such as the lack of data to ensure safe and effective dosing and the unavailability of these drugs in palatable suspensions," she said. "Although protease inhibitors appear promising, data substantiating the superiority of combinations containing protease inhibitors to nucleoside analogues in children are not yet available."
Numerous studies are under way that compare newer, possibly better combinations of drugs for children, Lim said.
In North Carolina, research nurse Virginia Dudek of UNC-CH also collaborated in the study, as did Drs. Ross E. McKinney and Karen O'Donnell, nurse Barbara Lane and physician?s associate Megan Valentine at Duke University.
Slightly more than 54 percent of the children were black, 30 percent were Hispanic, almost 14 percent were white, and the rest came from other racial or ethnic groups.
Glaxo-Wellcome Pharmaceuticals produces zidovudine, and Bristol-Myers Squibb Pharmaceuticals produces didanosine.
Note: Lim's number is (919) 966-2331. She can be paged by calling 966-4140 and entering 4906.
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