Major Pediatric Study Stopped Early: Combination Treatment Better

On June 26, the U.S. National Institute of Allergy and Infectious Diseases (NIAID) announced that it was stopping a clinical trial in over 600 children ahead of schedule, because those assigned to treatment with AZT plus 3TC did much better than those treated with ddI monotherapy. In this trial, known as ACTG 300, the risk of disease progression was reduced by about 70%, and the risk of death was reduced by about 80%, for those receiving the combination vs. those receiving the single drug. This result is mainly from children under 3 (who were analyzed separately), because there were far fewer cases of disease progression, and no deaths, in the children over 3, so reliable conclusions for them could not be drawn from this study. The children in ACTG 300 had symptomatic HIV disease, and little or no prior experience with antiretrovirals. Both treatment regimens were generally well tolerated.

Those who received a third treatment, AZT+ddI, also did better than those receiving ddI alone. But there is less information about AZT+ddI from this study, since that treatment arm was closed early to new enrollment, due to results from an earlier study (ACTG 152) suggesting that ddI alone was comparable to AZT+ddI. The differences between the two studies, and the reasons for the apparently conflicting results, are now being analyzed. Meanwhile, the ACTG 300 Abbreviated Executive Summary concludes: "In symptomatic antiviral naive HIV-infected children, combination therapy with either ZDV [AZT] plus 3TC or ZDV plus ddI was superior by clinical and laboratory measures to monotherapy with ddI, and therefore should be the preferred initial treatment, particularly for children under three years of age."

ACTG 300 began in July 1995 and was conducted at 87 medical centers in the United States; 65 of them were Federally supported (by NIAID, and by the U.S. National Institute of Child Health and Human Development), and 22 were supported by Glaxo Wellcome. Of the 596 children in the preliminary analysis which has been done so far, 42% were male, 63% were black, 22% were Hispanic, 14% were white, and 1% were from other ethnic groups.

Only very preliminary reports of the results are now available, as the data analysis which ended the study took place on June 18, 1997 -- only eight days before the public announcement that the study was being stopped. More will be learned as further analysis is completed.