A phase I study of abacavir (1592U89) alone and in combination with other antiretroviral agents in infants and children with human immunodeficiency virus infection. AIDS Clinical Trials Group 330 Team.

M. W. Kline, S. Blanchard, C. V. Fletcher, J. L. Shenep, R. E. McKinney, R. C. Brundage, M. Culnane, R. B. Van Dyke, W. M. Dankner, A. Kovacs, J. A. McDowell, S. Hetherington

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Abstract

OBJECTIVES: To evaluate the pharmacokinetic features, safety, and tolerance of abacavir, given alone and in combination with other nucleoside antiretroviral agents, in symptomatic human immunodeficiency virus (HIV)-infected children. METHODS: HIV-infected children discontinued prior antiretroviral therapy and were given abacavir orally, 4 mg/kg every 12 hours for 6 weeks, followed by 8 mg/kg every 12 hours for 6 weeks (n = 39); or 8 mg/kg every 12 hours for 12 weeks (n = 8). Children then were randomized to receive a second nucleoside antiretroviral agent (zidovudine, stavudine, didanosine, or lamivudine), plus abacavir. Pharmacokinetics, safety, tolerance, CD4(+) lymphocyte counts, and plasma HIV RNA concentrations were evaluated. RESULTS: At a dose of 8 mg/kg every 12 hours, area under the plasma concentration-versus-time curves and plasma half-life values were comparable with those reported for adults receiving abacavir at a dose of 300 mg twice daily. One case each of hypersensitivity reaction and peripheral neuropathy occurred during abacavir monotherapy. Three children experienced neutropenia while receiving abacavir in combination with another antiretroviral agent. Mean CD4(+) lymphocyte count and plasma HIV RNA concentration did not change when prior antiretroviral therapy was changed to abacavir monotherapy. CONCLUSIONS: Abacavir therapy is associated with good short-term tolerance and safety in HIV-infected children. Phase III studies are in progress to assess the antiviral activity of abacavir in children and adults.

Original languageEnglish (US)
Pages (from-to)e47
JournalPediatrics
Volume103
Issue number4
DOIs
StatePublished - Apr 1999

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Anti-Retroviral Agents
Virus Diseases
Acquired Immunodeficiency Syndrome
Clinical Trials
HIV
CD4 Lymphocyte Count
Safety
Nucleosides
Pharmacokinetics
RNA
Stavudine
Didanosine
abacavir
Zidovudine
Peripheral Nervous System Diseases
Neutropenia
Antiviral Agents
Half-Life
Hypersensitivity
Therapeutics

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health

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A phase I study of abacavir (1592U89) alone and in combination with other antiretroviral agents in infants and children with human immunodeficiency virus infection. AIDS Clinical Trials Group 330 Team. / Kline, M. W.; Blanchard, S.; Fletcher, C. V.; Shenep, J. L.; McKinney, R. E.; Brundage, R. C.; Culnane, M.; Van Dyke, R. B.; Dankner, W. M.; Kovacs, A.; McDowell, J. A.; Hetherington, S.

In: Pediatrics, Vol. 103, No. 4, 04.1999, p. e47.

Research output: Contribution to journalArticle

Kline, MW, Blanchard, S, Fletcher, CV, Shenep, JL, McKinney, RE, Brundage, RC, Culnane, M, Van Dyke, RB, Dankner, WM, Kovacs, A, McDowell, JA & Hetherington, S 1999, 'A phase I study of abacavir (1592U89) alone and in combination with other antiretroviral agents in infants and children with human immunodeficiency virus infection. AIDS Clinical Trials Group 330 Team.', Pediatrics, vol. 103, no. 4, pp. e47. https://doi.org/10.1542/peds.103.4.e47
Kline, M. W. ; Blanchard, S. ; Fletcher, C. V. ; Shenep, J. L. ; McKinney, R. E. ; Brundage, R. C. ; Culnane, M. ; Van Dyke, R. B. ; Dankner, W. M. ; Kovacs, A. ; McDowell, J. A. ; Hetherington, S. / A phase I study of abacavir (1592U89) alone and in combination with other antiretroviral agents in infants and children with human immunodeficiency virus infection. AIDS Clinical Trials Group 330 Team. In: Pediatrics. 1999 ; Vol. 103, No. 4. pp. e47.
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abstract = "OBJECTIVES: To evaluate the pharmacokinetic features, safety, and tolerance of abacavir, given alone and in combination with other nucleoside antiretroviral agents, in symptomatic human immunodeficiency virus (HIV)-infected children. METHODS: HIV-infected children discontinued prior antiretroviral therapy and were given abacavir orally, 4 mg/kg every 12 hours for 6 weeks, followed by 8 mg/kg every 12 hours for 6 weeks (n = 39); or 8 mg/kg every 12 hours for 12 weeks (n = 8). Children then were randomized to receive a second nucleoside antiretroviral agent (zidovudine, stavudine, didanosine, or lamivudine), plus abacavir. Pharmacokinetics, safety, tolerance, CD4(+) lymphocyte counts, and plasma HIV RNA concentrations were evaluated. RESULTS: At a dose of 8 mg/kg every 12 hours, area under the plasma concentration-versus-time curves and plasma half-life values were comparable with those reported for adults receiving abacavir at a dose of 300 mg twice daily. One case each of hypersensitivity reaction and peripheral neuropathy occurred during abacavir monotherapy. Three children experienced neutropenia while receiving abacavir in combination with another antiretroviral agent. Mean CD4(+) lymphocyte count and plasma HIV RNA concentration did not change when prior antiretroviral therapy was changed to abacavir monotherapy. CONCLUSIONS: Abacavir therapy is associated with good short-term tolerance and safety in HIV-infected children. Phase III studies are in progress to assess the antiviral activity of abacavir in children and adults.",
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AU - Blanchard, S.

AU - Fletcher, C. V.

AU - Shenep, J. L.

AU - McKinney, R. E.

AU - Brundage, R. C.

AU - Culnane, M.

AU - Van Dyke, R. B.

AU - Dankner, W. M.

AU - Kovacs, A.

AU - McDowell, J. A.

AU - Hetherington, S.

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N2 - OBJECTIVES: To evaluate the pharmacokinetic features, safety, and tolerance of abacavir, given alone and in combination with other nucleoside antiretroviral agents, in symptomatic human immunodeficiency virus (HIV)-infected children. METHODS: HIV-infected children discontinued prior antiretroviral therapy and were given abacavir orally, 4 mg/kg every 12 hours for 6 weeks, followed by 8 mg/kg every 12 hours for 6 weeks (n = 39); or 8 mg/kg every 12 hours for 12 weeks (n = 8). Children then were randomized to receive a second nucleoside antiretroviral agent (zidovudine, stavudine, didanosine, or lamivudine), plus abacavir. Pharmacokinetics, safety, tolerance, CD4(+) lymphocyte counts, and plasma HIV RNA concentrations were evaluated. RESULTS: At a dose of 8 mg/kg every 12 hours, area under the plasma concentration-versus-time curves and plasma half-life values were comparable with those reported for adults receiving abacavir at a dose of 300 mg twice daily. One case each of hypersensitivity reaction and peripheral neuropathy occurred during abacavir monotherapy. Three children experienced neutropenia while receiving abacavir in combination with another antiretroviral agent. Mean CD4(+) lymphocyte count and plasma HIV RNA concentration did not change when prior antiretroviral therapy was changed to abacavir monotherapy. CONCLUSIONS: Abacavir therapy is associated with good short-term tolerance and safety in HIV-infected children. Phase III studies are in progress to assess the antiviral activity of abacavir in children and adults.

AB - OBJECTIVES: To evaluate the pharmacokinetic features, safety, and tolerance of abacavir, given alone and in combination with other nucleoside antiretroviral agents, in symptomatic human immunodeficiency virus (HIV)-infected children. METHODS: HIV-infected children discontinued prior antiretroviral therapy and were given abacavir orally, 4 mg/kg every 12 hours for 6 weeks, followed by 8 mg/kg every 12 hours for 6 weeks (n = 39); or 8 mg/kg every 12 hours for 12 weeks (n = 8). Children then were randomized to receive a second nucleoside antiretroviral agent (zidovudine, stavudine, didanosine, or lamivudine), plus abacavir. Pharmacokinetics, safety, tolerance, CD4(+) lymphocyte counts, and plasma HIV RNA concentrations were evaluated. RESULTS: At a dose of 8 mg/kg every 12 hours, area under the plasma concentration-versus-time curves and plasma half-life values were comparable with those reported for adults receiving abacavir at a dose of 300 mg twice daily. One case each of hypersensitivity reaction and peripheral neuropathy occurred during abacavir monotherapy. Three children experienced neutropenia while receiving abacavir in combination with another antiretroviral agent. Mean CD4(+) lymphocyte count and plasma HIV RNA concentration did not change when prior antiretroviral therapy was changed to abacavir monotherapy. CONCLUSIONS: Abacavir therapy is associated with good short-term tolerance and safety in HIV-infected children. Phase III studies are in progress to assess the antiviral activity of abacavir in children and adults.

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