A phase I/II study of the protease inhibitor ritonavir in children with human immunodeficiency virus infection PEDIATRICS Mueller, B. U., Nelson, R. P., Sleasman, J., Zuckerman, J., Heath-Chiozzi, M., STEINBERG, S. M., BALIS, F. M., Brouwers, P., Hsu, A., Saulis, R., Sei, S., Wood, L. V., Zeichner, S., Katz, T. T., Higham, C., Aker, D., Edgerly, M., Jarosinski, P., Serchuck, L., WHITCUP, S. M., Pizzuti, D., Pizzo, P. A. 1998; 101 (3): 335-343

Abstract

Ritonavir, a potent antiretroviral protease inhibitor, has been approved for the treatment of adults and children with human immunodeficiency virus (HIV) infection. In a phase I/II study, we assessed the safety, tolerability, and pharmacokinetic profile of the oral solution of ritonavir in HIV-infected children and studied the preliminary antiviral and clinical effects.HIV-infected children between 6 months and 18 years of age were eligible. Four dose levels of ritonavir oral solution (250, 300, 350, and 400 mg/m given every 12 hours) were evaluated in two age groups (2 years). Ritonavir was administered alone for the first 12 weeks and then in combination with zidovudine and/or didanosine. Clinical and laboratory parameters were monitored every 2 to 4 weeks.A total of 48 children (median age, 7.7 years; range, 0.5 to 14.4 years) were included in this analysis. Dose-related nausea, diarrhea, and abdominal pain were the most common toxicities and resulted in discontinuation of ritonavir in 7 children. Ritonavir was well absorbed at all dose levels, and plasma concentrations reached a peak 2 to 4 hours after a dose. CD4 cells counts increased by a median of 79 cells/mm3 after 4 weeks of monotherapy and were maintained throughout the study. Plasma HIV RNA decreased by 1 to 2 log10 copies/mL within 4 to 8 weeks of ritonavir monotherapy, and this level was sustained in patients enrolled at the highest dose level of 400 mg/m for the 24-week period.The oral solution of ritonavir has potent antiretroviral activity as a single agent and is relatively well tolerated by children when administered alone or in combination with zidovudine or didanosine.

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View details for PubMedID 9480994