ACTG 152: Efficacy and Safety Study Results

Date: February 28, 1996
Source: National Institutes of Health (NIH)
Author: National Institute of Allergy and Infectious Diseases (NIAID)

Final results from a large study comparing three treatments for children with symptomatic HIV infection or AIDS showed that treatments with either didanosine (ddI) alone or a combination of ddI plus zidovudine (AZT) were equally efficacious. Both treatment regimens were more effective than AZT alone as initial therapy to prevent disease progression including death. These findings complement the results from adult studies comparing antiretrovirals given alone and in combination.

The trial, AIDS Clinical Trials Group (ACTG) 152, compared AZT alone, ddI alone and a combination of AZT and ddI in children with symptomatic HIV infection aged 3 months to 18 years who had received little or no prior antiretroviral treatment.

The study was a collaborative effort conducted by the Pediatric ACTG and funded by the National Institute of Allergy and Infectious Diseases and the National Institute of Child health and Human Development. The study's protocol chairs were 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. (now Glaxo-Wellcome) provided the AZT for the study.

These are important findings from the largest controlled pediatric HIV trial to date. The results add significantly to our knowledge of therapy for children with HIV disease, "says Anthony S. Fauci, M.C., director of NIAID.

The study, which opened in August 1991 and enrolled the last patient in August 1993, included 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 was conducted at 78 sites funded by NIAID and NICHD. Neither the doctors, the patients, nor the parents knew which therapy each child received.

Interim analyses presented to the NIAID Data and Safety Monitoring Board in February 1995 indicated that AZT alone was less effective than the best of the other two treatment arms and was associated with more side effects. The AZT arm of therapy was then stopped. The study continued to evaluate the remaining two treatment arms until August 1995 when the last enrolled child would have been followed for two years on protocol.

Final analyses of the ACTG 152 study assessed whether there were differences in effectiveness and toxicity between treatment with ddI alone and with a combination of ddI and AZT. Both ddI and combination AZT plus ddI were equally effective in preventing or delaying certain clinical outcomes. These outcomes included impaired weight gain, developmental and neurologic problems, new or recurrent opportunistic infection, malignancy and death. Fewer toxicities were seen in children receiving ddI monotherapy, although in general, side effects such as anemia or low white blood counts were easily manageable for both AZT and ddI recipients.

Because ACTG 152 evaluated only HIV-infected children with little or no prior antiretroviral therapy, these findings cannot be generalized to children who have already received antiretroviral therapy. Further research is needed to evaluate the relative efficacy of monotherapy versus combination therapy among children with prior antiretroviral experience.

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 12,000 children are infected with HIV in the United States.

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 U.S. Department of Health and Human Services.

Prepared by:
Office of Communications National Institute of Allergy and Infectious Diseases National Institutes of Health Bethesda, MD 20892
U.S. Public Health Service U.S. Department of Health and Human Services