Pharmacokinetics and acceptability of once- versus twice-daily lamivudine and abacavir in HIV type-1-infected Ugandan children in the ARROW Trial.
Abstract
Background: No data on once-daily dosing of nucleoside analogues in African children currently exist. We compared the pharmacokinetics (PK) of once- versus twice-daily lamivudine and abacavir treatment using the World Health Organization recommended weight band dosing of scored adult tablets. Methods: HIV type-1 (HIV-1)-infected Ugandan children aged 3-12 years receiving antiretroviral therapy that included lamivudine and abacavir twice daily (total 150+300 mg, 225+450 mg and 225/300+600 mg daily for children weighing 12-0-24) and maximum concentrations (C<sub>max</sub>) were compared by geometric mean ratios (GMRs). Results: A total of 41 HIV-1-infected children (median age of 7 years; n=23, n=14 and n=4 in the 12-0-24 was 13.0 and 12.0 mg•h/l for once- and twice-daily lamivudine (GMR 1.09, 90% confidence intervals [CI] 0.98-1.20) and 15.3 and 15.6 mg•h/l for once- and twice-daily abacavir (GMR 0.98, 90% CI 0.89-1.08), respectively, with no difference between 3-6 and 7-12 year olds. C<sub>max</sub> was 76% (lamivudine) and 64% (abacavir) higher on once-daily regimens. For both children and caregivers, once-daily dosing of lamivudine plus abacavir was highly acceptable and strongly preferred over twice-daily. Conclusions: In children aged 3-12 years, AUC<sub>0-24</sub> of lamivudine and abacavir were bioequivalent on once- and twice-daily regimens. Once-daily dosing of abacavir and lamivudine could provide an alternative dosing strategy for HIV-1-infected children, with high acceptability and strong preference suggesting the potential for improved adherence.
Citation
Antiviral Therapy (2010) 15 (8) 1115-1124 [doi:10.3851/IMP1695]