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

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/mm3 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/m2 BID; ABC/3TC/ZDV group) or ABC placebo plus 3TC (4 mg/kg BID) and ZDV (180 mg/m2; 3TC/ZDV group). Participants who met a protocol-defined switch criteria (plasma HIV-1 RNA >0.5 log10 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.