Pharmacokinetics and tolerability of once- versus twice-daily lopinavir/ritonavir treatment in HIV-1-infected children

Abstract

Background

Once-daily lopinavir/ritonavir (LPV/r) is not approved for treatment of HIV paediatric patients. Once daily treatment in children might serve the same goals of patient comfort and adherence as in adults.

Methods

HIV type-1-infected children aged 6 months to 18 years, who were virologically suppressed on an LPV/r-containing regimen, were eligible. Treatment 1 consisted of once-daily LPV/r 460/115 mg/m², plus two nucleoside reverse transcriptase inhibitors (NRTIs). Treatment 2 consisted of twice-daily LPV/r 230/57.5 mg/m² plus two NRTIs. Patients were randomized either to start with treatment 1 followed by treatment 2 or vice versa. Full pharmaco-kinetic profiles were analysed for lopinavir and ritonavir with a validated HPLC tandem mass spectrometry assay.

Results

Seven patients (five girls and two boys) were included in the study. Median age was 9.8 years (range 5.8–15.5). For the once-daily treatment, the median (range) lopinavir 24 h area under the plasma concentration–time curve (AUC_24h), maximum plasma concentration (C_max) and 24 h plasma concentration (C_24h) were 214.6 h•mg/l (114.2–289.2), 13.5 mg/l (8.3–17.5) and 3.4 mg/l (0.6–7.4), respectively. For the twice-daily treatment the median (range) lopinavir 12 h area under the plasma concentration–time curve (AUC_12h), C_max and 12 h plasma concentration (C_12h) were 80.9 h•mg/l (23.3–135.9), 9.8 mg/l (3.4–15.2) and 5.7 mg/l (1.7– 9.7), respectively.

Conclusions

This study suggests that the pharmacokinetics of lopinavir after twice-daily and once-daily dosing are similar, with no observable difference in tolerability, in this group of patients between 5 and 15 years old.