Once- versus twice-daily lopinavir/ritonavir tablets in virologically suppressed, HIV-infected, treatment-experienced children: comparative pharmacokinetics and virological outcome after switching to once-daily lopinavir/ritonavir.

OBJECTIVES

Data on lopinavir/ritonavir tablets administered once daily in children are limited. We compared the pharmacokinetics (PK) of lopinavir/ritonavir twice daily versus once daily in virologically suppressed, HIV-infected children, and assessed the virological outcome, at 48 weeks, in children receiving the regimen of lopinavir/ritonavir once daily.

PATIENTS AND

METHODS

HIV-infected children receiving a twice-daily lopinavir/ritonavir-based regimen and with an HIV-1 RNA viral load (VL) <40 copies/mL for at least 3 months were enrolled. Intensive steady-state 12 h blood sampling for PK assessment was performed at enrolment. Immediately afterwards, the lopinavir/ritonavir dose was changed to once daily with the equivalent daily dose, and intensive steady-state 24 h blood sampling was repeated 2 weeks later. If the lopinavir C(trough) was <1.0 μg/mL, the lopinavir/ritonavir dose was increased by 20%-30% and C(trough) measurement repeated. CD4 cell counts and VL were determined at baseline and at 12, 24 and 48 weeks.

RESULTS

Twelve children were enrolled. The median age was 13.1 years. Lopinavir AUC(0-24) following twice-daily and once-daily dosing was 169.7 (124.0-200.8) and 167.1 (95.1-228.1) μg · h/mL, respectively. Seven children, including all six concomitantly receiving efavirenz, had a C(trough) <1.0 μg/mL with once-daily lopinavir/ritonavir dosing, and four of seven children had a C(trough) <1.0 μg/mL after dose adjustment. All children maintained virological suppression throughout the 48 week period.

CONCLUSIONS

Lopinavir/ritonavir-based once-daily regimens could simplify therapy in children/adolescents with virological control, but a lower lopinavir C(trough) was evident. Further efficacy studies of lopinavir/ritonavir once daily in children are necessary before routinely recommending this dosing strategy.