A randomized, double-blind study of triple nucleoside therapy of abacavir, lamivudine, and zidovudine versus lamivudine and zidovudine in previously treated human immunodeficiency virus type 1-infected children. The CNAA3006 Study Team.

X. Sáez-Llorens, Robert Nelson, P. Emmanuel, A. Wiznia, C. Mitchell, J. A. Church, J. Sleasman, R. Van Dyke, C. G. Richardson, A. Cutrell, W. Spreen, S. Hetherington

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Abstract

OBJECTIVES: Abacavir (ABC) is a potent inhibitor of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase. We compared the efficacy, safety, and tolerability of combination therapy with ABC, lamivudine (3TC), and zidovudine (ZDV) versus 3TC and ZDV in antiretroviral experienced HIV-1-infected children over 48 weeks. METHODS: Two hundred five HIV-1-infected children who had received previous antiretroviral therapy and had CD4(+) cell counts >/=100 cells/mm(3) were stratified by age and by previous treatment. Participants were randomly assigned to receive ABC (8 mg/kg twice daily [BID]) plus 3TC (4 mg/kg BID) and ZDV (180 mg/m(2) BID; ABC/3TC/ZDV group) or ABC placebo plus 3TC (4 mg/kg BID) and ZDV (180 mg/m(2); 3TC/ZDV group). Participants who met a protocol-defined switch criteria (plasma HIV-1 RNA >0.5 log(10) copies/mL above baseline at week 8 or >10 000 copies/mL after week 16) had the option to switch to open-label ABC plus any antiretroviral combination or continue randomized therapy or withdraw from the study. RESULTS: The Kaplan-Meier estimates (95% confidence interval) of the proportion of participants who maintained HIV-1 RNA levels </=10 000 copies/mL for 48 weeks or more was significantly better in the ABC/3TC/ZDV group compared with the 3TC/ZDV group: 33% (23%-42%) versus 21% (13%-29%). At week 48, the proportions of participants with HIV-1 RNA </=10 000 copies/mL were 36% versus 26% for the ABC/3TC/ZDV and 3TC/ZDV groups, respectively, by intent-to-treat analysis. For the subgroup of participants with baseline HIV-1 RNA >10 000 copies/mL, a significantly higher proportion of participants in the ABC/3TC/ZDV group had HIV-1 RNA </=10 000 copies/mL compared with the 3TC/ZDV group (29% vs 12%) but no difference was observed in the subgroup of participants with baseline HIV-1 RNA </=10 000 copies/mL (78% vs 72%). The median changes from baseline in CD4(+) cell counts were greater in the ABC/3TC/ZDV group than in the 3TC/ZDV group. Few participants (3%) experienced abacavir-related hypersensitivity reaction. CONCLUSIONS: ABC, in combination with 3TC and ZDV, provides additional antiretroviral activity over 48 weeks, compared with combination therapy with 3TC and ZDV in antiretroviral experienced HIV-1-infected children. ABC was safe and generally well-tolerated and should be considered an active component of combination antiretroviral therapy in this pediatric population.

Original languageEnglish (US)
JournalPediatrics
Volume107
Issue number1
StatePublished - Jan 2001
Externally publishedYes

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Lamivudine
Zidovudine
Nucleosides
Double-Blind Method
HIV-1
Therapeutics
RNA
CD4 Lymphocyte Count
lamivudine drug combination abacavir
abacavir
Kaplan-Meier Estimate
Hypersensitivity
Placebos

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health

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A randomized, double-blind study of triple nucleoside therapy of abacavir, lamivudine, and zidovudine versus lamivudine and zidovudine in previously treated human immunodeficiency virus type 1-infected children. The CNAA3006 Study Team. / Sáez-Llorens, X.; Nelson, Robert; Emmanuel, P.; Wiznia, A.; Mitchell, C.; Church, J. A.; Sleasman, J.; Van Dyke, R.; Richardson, C. G.; Cutrell, A.; Spreen, W.; Hetherington, S.

In: Pediatrics, Vol. 107, No. 1, 01.2001.

Research output: Contribution to journalArticle

Sáez-Llorens, X, Nelson, R, Emmanuel, P, Wiznia, A, Mitchell, C, Church, JA, Sleasman, J, Van Dyke, R, Richardson, CG, Cutrell, A, Spreen, W & Hetherington, S 2001, 'A randomized, double-blind study of triple nucleoside therapy of abacavir, lamivudine, and zidovudine versus lamivudine and zidovudine in previously treated human immunodeficiency virus type 1-infected children. The CNAA3006 Study Team.', Pediatrics, vol. 107, no. 1.
Sáez-Llorens, X. ; Nelson, Robert ; Emmanuel, P. ; Wiznia, A. ; Mitchell, C. ; Church, J. A. ; Sleasman, J. ; Van Dyke, R. ; Richardson, C. G. ; Cutrell, A. ; Spreen, W. ; Hetherington, S. / A randomized, double-blind study of triple nucleoside therapy of abacavir, lamivudine, and zidovudine versus lamivudine and zidovudine in previously treated human immunodeficiency virus type 1-infected children. The CNAA3006 Study Team. In: Pediatrics. 2001 ; Vol. 107, No. 1.
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AU - Nelson, Robert

AU - Emmanuel, P.

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AU - Mitchell, C.

AU - Church, J. A.

AU - Sleasman, J.

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