Pharmacokinetics of a Once-Daily Regimen of Lopinavir/Ritonavir in HIV-1-Infected Children

Abstract

Introduction

Lopinavir is an HIV protease inhibitor that is co-formulated with ritonavir. The approved paediatric dose is 230/57.5 mg/m² twice daily. Once-daily dosing may offer an advantage to adherence. We studied the pharmacokinetics of lopinavir/ritonavir in a once-daily regimen in HIV-1-infected children.

Methods

HIV-1-infected children on stable antiretroviral therapy with a viral load <50 copies/ml for at least 6 months received lopinavir/ritonavir 460/115 mg/m² once daily with zidovudine and lamivudine. Blood samples were collected at 0, 2, 4, 6, 8, 12, 18 and 24 h after observed intake during steady state. Target level for lopinavir C_min was 1.0 mg/l, based on in vitro IC₅₀ data.

Results

Nineteen HIV-1-infected children with a median (range) age of 4.5 (1.4–12.9) years were enrolled. The median (interquartile range) dose of lopinavir was 456 (444–477) mg/m². The mean (standard deviation) AUC_0–24, C_max and C_min of lopinavir were 149.8 ±58.8 h*mg/l, 10.77 ±2.90 mg/l and 2.88 ±3.74 mg/l respectively. These values are comparable to data observed in adults using lopinavir/ritonavir 800/200 mg once daily. In 10/19 (53%) children C_min was considered to be too low (<1.0 mg/l). Younger children more often experienced subtherapeutic trough levels.

Conclusion

Our findings indicate that 460/115 mg/m² lopinavir/ritonavir once daily leads to mean pharmacokinetic parameters comparable to data of 800/200 mg lopinavir/ritonavir once daily in adults, although the variability observed in the trough levels is much higher in children. Further research, especially in young children, is necessary to determine whether a higher dosage of lopinavir/ritonavir once daily must be given to reach the target level for C_min.