A phase I/II study of the protease inhibitor ritonavir in children with human immunodeficiency virus infection.

Journal Article (Clinical Trial;Journal Article)

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Full Text

Duke Authors

Cited Authors

  • Mueller, BU; Nelson, RP; Sleasman, J; Zuckerman, J; Heath-Chiozzi, M; Steinberg, SM; Balis, FM; Brouwers, P; Hsu, A; Saulis, R; Sei, S; Wood, LV; Zeichner, S; Katz, TT; Higham, C; Aker, D; Edgerly, M; Jarosinski, P; Serchuck, L; Whitcup, SM; Pizzuti, D; Pizzo, PA

Published Date

  • March 1, 1998

Published In

Volume / Issue

  • 101 / 3 Pt 1

Start / End Page

  • 335 - 343

PubMed ID

  • 9480994

International Standard Serial Number (ISSN)

  • 0031-4005

Digital Object Identifier (DOI)

  • 10.1542/peds.101.3.335


  • eng

Conference Location

  • United States