RANDOMIZED STUDY OF 2 DOSES OF DIDANOSINE IN CHILDREN INFECTED WITH HUMAN-IMMUNODEFICIENCY-VIRUS

2'3'-Dideoxyinosine (didanosine) is a nucleoside analog active in vitr o against human immunodeficiency virus. Few data are available regardi ng its use for the treatment of children. In a single-center, randomiz ed, open-label trial, we compared two dosages of didanosine (120 vs 27 0 mg/m2 per day) for at least 6 months in 34 children infected with hu man immunodeficiency virus who had become resistant to or were intoler ant of zidovudine. Serum levels of didanosine 1 hour after administrat ion were significantly different in the two groups and remained stable with time. There was a significant reduction in human immunodeficienc y virus-p24 antigenemia and quantitative cellular viremia with time bu t no difference between the two groups. The intensity of the biologic response, however, was significantly higher in the patients who had mo re than 50 CD4+ cells 10(6)/L at inclusion. No pancreatic or neurologi c toxic effects were observed. In five children, liver function abnorm alities developed that are unusual in this setting, and the death of o ne child from unexplained hepatocellular failure suggests that didanos ine may be hepatotoxic. Three of these five children had preexisting l iver disease. Although no definite conclusion can be made as to the op timal dose, there were no major differences between the two administra tion schedules in terms of biologic effects and tolerability.