934    

Background:  Little is known on once daily use of nucleoside analogues in HIV⁺ children. This study compared the plasma pharmacokinetics of once daily with twice daily lamivudine (3TC) (8 mg/kg once daily vs 4 mg/kg twice daily) and abacavir (ABC) (16 mg/kg once daily vs 8 mg/kg twice daily) in HIV⁺ children. Final results are presented.

Methods:  HIV⁺ children ³2 to <13 years old receiving combination treatment containing 3TC and/or ABC twice daily were included in this one arm, open label cross-over study. Intensive plasma pharmacokinetic sampling was performed at steady state, after which children switched to taking their 3TC and/or ABC once daily. Pharmacokinetic sampling was repeated at steady state. Daily area under the curve (AUC_0-24) and peak level (C_max) of once daily and twice daily regimens were compared by geometric mean ratios (GMR) with 90% confidence intervals (CI).

Results:  We enrolled 24 children, of whom 20 (median age 5.6 years [range 2.1 to 12.8]) had evaluable pharmacokinetic data of 3TC (N = 19) and/or ABC (n = 14). AUC_0-24 and C_max  (GM [90% CI]) of 3TC were 8.88 (7.67 to 10.28) mg/L*h and 1.11 (0.96 to 1.29) mg/L for twice daily, and 9.80 (8.64 to 11.12) mg/L*h and 2.09 (1.80 to 2.42) mg/L for once daily, respectively. C_min of 3TC (median) was 0.067 and 0.050 mg/L, respectively, for once daily and twice daily regimens. AUC_0-24 and C_max of ABC (GM [90% CI]) were 9.91 (8.26 to 11.89) mg/L*h and 2.14 (1.79 to 2.56) mg/L, for twice daily, and 13.37 (11.80 to 15.16) mg/L*h and 4.80 (4.04 to 5.71) mg/L for once daily, respectively. C_min of ABC (median) was 0.025 and < 0.015 mg/L, respectively, for twice daily and once daily regimens. GMR of 3TC and ABC AUC_0-24 and C_max once daily vs twice daily significantly exceeded 1.0 (see Table). GMR were not significantly different between children aged ³2 to 6 and >6 to <13 years (p >0.08).

Conclusions:  In HIV⁺ children, AUC_0-24 and C_max of both 3TC and ABC once daily were not inferior to twice daily regimens. The roughly similar AUC_0-24, and twice higher C_max of 3TC once daily vs twice daily suggest dose-proportional pharmacokinetics of 3TC. For ABC once daily, the tendency to increased AUC_0-24 and more than 2 times increased C_max with regard to twice daily may reflect slightly more than dose-proportional pharmacokinetic. In view of their relatively good tolerance and promising data on once daily use of 3TC and ABC in adults, these results suggest feasibility of once daily use of these agents in HIV⁺ children. Therapeutic equivalence should be further evaluated in a comparative clinical trial.

Keywords: pharmacokinetics; lamivudine; abacavir