Interim Results Lead to Discontinuation of AZT-Only Study Arm
Interim results of a study comparing three treatments for children with symptomatic HIV infection or AIDS showed that zidovudine (AZT) alone was the least effective as an initial therapy to prevent disease progression. The children receiving AZT as a single agent also had higher rates of side effects.
The trial, AIDS Clinical Trials Group (ACTG) 152 compares AZT alone, didanosine (ddI) alone and a combination of AZT and ddI in children with AIDS aged 3 months to 18 years who had received little or no prior antiretroviral treatment. Investigators will continue the study without the single agent AZT arm.
The study is a collaborative effort by the Pediatric ACTG of the National Institute of Allergy and Infectious Diseases and the National Institute of Child Health and Human Development. The study's protocol chairs are Carol J. Baker, M.D., and Janet Englund, M.D., both from the Baylor College of Medicine, Houston, Texas. Bristol-Myers Squibb provided the ddI and the Burroughs Wellcome Co. provided the AZT for the study.
An independent data and safety monitoring board reviewed the interim data from the study and recommended that the single agent AZT arm be discontinued. Because differences in disease progression and side effects between the other two arms were not significant, the ddI and the ddI/AZT combination arms will continue.
These interim results add to our knowledge base of therapy for children with HIV disease. Further clarification of options for treatment will emerge as additional study data are accumulated and analyzed," says Anthony S. Fauci, M.D., NIAID director.
Children who received AZT alone will be offered the option of switching to another therapy or continuing on AZT, whichever is appropriate for the individual child's condition.
Under ACTG 152, neither the doctors nor the patients knew which therapy each patient received. However, the monitoring board's review revealed that the group of children receiving AZT alone had more rapid rates of disease progression as measured by growth failure, new opportunistic infections, neurologic and neurodevelopmental deterioration or death. The major side effects seen in the study were blood and other chemical abnormalities. Children receiving AZT monotherapy had a significantly higher proportion of these side effects.
The study, which opened in August 1991 and enrolled the last patient in August 1993, includes 839 children, who were 3 months to 18 years when enrolled, with 54 percent of the total aged 3 months to 30 months. The study is conducted at 35 NIAID-funded sites and 26 NICHD-funded sites and one regional center of the National Hemophilia Foundation, funded by NIAID.
Further analysis of the study, including determination of any differences in effectiveness and toxicity between treatment with ddI and with a combination of ddI and AZT, will take place in late 1995 after the study closes.
HIV disease is the fifth leading cause of death in U.S. children younger than 15 years, according to the National Center for Health Statistics. An estimated 10,000 children are infected with HIV in the United States, with about 1,750 new infections occurring each year.
NIAID and NICHD, two of the 17 institutes at the National Institutes of Health, support scientists and scientific studies at universities, medical schools and research institutions in the United States and abroad. NIH is an agency of the U.S. Public Health Service, part of the Department of Health and Human Services.