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

Brigitta U. Mueller, Robert P. Nelson, John Sleasman, Judy Zuckerman, Margo Heath-Chiozzi, Seth M. Steinberg, Frank M. Balis, Pim Brouwers, Ann Hsu, Rima Saulis, Shizuko Sei, Lauren V. Wood, Steve Zeichner, T. Teresa K. Katz, Colleen Higham, Diane Aker, Maureen Edgerly, Paul Jarosinski, Leslie Serchuck, Scott M. WhitcupDavid Pizzuti, Philip A. Pizzo

Research output: Contribution to journalArticle

72 Scopus citations


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/m2 given every 12 hours) were evaluated in two age groups (≤2 years, >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/m2 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.

Original languageEnglish (US)
Pages (from-to)335-343
Number of pages9
Issue number3 I
StatePublished - Mar 1998


  • CD4 cells
  • Child
  • HIV-1
  • Pharmacokinetics
  • Protease inhibitor

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health

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    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. K., Higham, C., Aker, D., Edgerly, M., Jarosinski, P., Serchuck, L., ... Pizzo, P. A. (1998). A phase I/II study of the protease inhibitor Ritonavir in children with human immunodeficiency virus infection. Pediatrics, 101(3 I), 335-343. https://doi.org/10.1542/peds.101.3.335