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

Brigitta U. Mueller, Robert 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 Citations (Scopus)

Abstract

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
JournalPediatrics
Volume101
Issue number3 I
DOIs
StatePublished - Mar 1998
Externally publishedYes

Fingerprint

Ritonavir
Virus Diseases
Protease Inhibitors
HIV
Didanosine
Zidovudine
Protease
AIDS/HIV
CD4 Lymphocyte Count
Dose
Nausea
Abdominal Pain
Antiviral Agents
Diarrhea
Pharmacokinetics
Age Groups
RNA
Safety

Keywords

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

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Medicine(all)
  • Arts and Humanities (miscellaneous)

Cite this

Mueller, B. U., Nelson, R., Sleasman, J., Zuckerman, J., Heath-Chiozzi, M., Steinberg, S. M., ... 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

A phase I/II study of the protease inhibitor Ritonavir in children with human immunodeficiency virus infection. / Mueller, Brigitta U.; Nelson, Robert; Sleasman, John; Zuckerman, Judy; Heath-Chiozzi, Margo; Steinberg, Seth M.; Balis, Frank M.; Brouwers, Pim; Hsu, Ann; Saulis, Rima; Sei, Shizuko; Wood, Lauren V.; Zeichner, Steve; Katz, T. Teresa K; Higham, Colleen; Aker, Diane; Edgerly, Maureen; Jarosinski, Paul; Serchuck, Leslie; Whitcup, Scott M.; Pizzuti, David; Pizzo, Philip A.

In: Pediatrics, Vol. 101, No. 3 I, 03.1998, p. 335-343.

Research output: Contribution to journalArticle

Mueller, BU, Nelson, R, Sleasman, J, Zuckerman, J, Heath-Chiozzi, M, Steinberg, SM, Balis, FM, Brouwers, P, Hsu, A, Saulis, R, Sei, S, Wood, LV, Zeichner, S, Katz, TTK, Higham, C, Aker, D, Edgerly, M, Jarosinski, P, Serchuck, L, Whitcup, SM, Pizzuti, D & Pizzo, PA 1998, 'A phase I/II study of the protease inhibitor Ritonavir in children with human immunodeficiency virus infection', Pediatrics, vol. 101, no. 3 I, pp. 335-343. https://doi.org/10.1542/peds.101.3.335
Mueller, Brigitta U. ; Nelson, Robert ; Sleasman, John ; Zuckerman, Judy ; Heath-Chiozzi, Margo ; Steinberg, Seth M. ; Balis, Frank M. ; Brouwers, Pim ; Hsu, Ann ; Saulis, Rima ; Sei, Shizuko ; Wood, Lauren V. ; Zeichner, Steve ; Katz, T. Teresa K ; Higham, Colleen ; Aker, Diane ; Edgerly, Maureen ; Jarosinski, Paul ; Serchuck, Leslie ; Whitcup, Scott M. ; Pizzuti, David ; Pizzo, Philip A. / A phase I/II study of the protease inhibitor Ritonavir in children with human immunodeficiency virus infection. In: Pediatrics. 1998 ; Vol. 101, No. 3 I. pp. 335-343.
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abstract = "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.",
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T1 - A phase I/II study of the protease inhibitor Ritonavir in children with human immunodeficiency virus infection

AU - Mueller, Brigitta U.

AU - Nelson, Robert

AU - Sleasman, John

AU - Zuckerman, Judy

AU - Heath-Chiozzi, Margo

AU - Steinberg, Seth M.

AU - Balis, Frank M.

AU - Brouwers, Pim

AU - Hsu, Ann

AU - Saulis, Rima

AU - Sei, Shizuko

AU - Wood, Lauren V.

AU - Zeichner, Steve

AU - Katz, T. Teresa K

AU - Higham, Colleen

AU - Aker, Diane

AU - Edgerly, Maureen

AU - Jarosinski, Paul

AU - Serchuck, Leslie

AU - Whitcup, Scott M.

AU - Pizzuti, David

AU - Pizzo, Philip A.

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N2 - 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.

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KW - CD4 cells

KW - Child

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KW - Pharmacokinetics

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