Pharmacokinetics of lopinavir/ritonavir in second-line treatment of children with HIV in the CHAPAS-4 trial

Abstract

OBJECTIVE: Lopinavir/ritonavir (LPV/r) remains a much used drug combination for treatment of children with HIV, but pharmacokinetic data when the adult formulation (LPV/r 200/50 mg) is used for children weighing 25-34.9 kg, or when combined with tenofovir alafenamide/emtricitabine (TAF/FTC), is currently lacking. DESIGN: We aim to provide this data by an intensive LPV/r pharmacokinetic sub-study nested within the CHAPAS-4 trial (#ISRCTN22964075). METHODS: Children (3-15 years), weighing 14-24.9 kg received 200/50 mg LPV/r orally twice daily; those weighing 25-34.9 kg received 400/100 mg LPV/r in the morning and 200/50 mg in the evening; and those weighing at least 35 kg received 400/100 mg LPV/r twice daily. LPV/r was used in combination with either TAF/FTC or standard-of-care backbone (abacavir/lamivudine or zidovudine/lamivudine). Pharmacokinetic parameters were compared to those reported in children receiving WHO-recommended dosages. RESULTS: We enrolled 40 children from Uganda, Zambia, and Zimbabwe. The geometric mean area under the concentration-time curve (AUC 0-12h ) for LPV was 116.2 h mg/l [coefficient of variation (CV%), 37%], comparable to children receiving WHO-recommended dosages. The geometric mean trough concentration was 7.7 mg/l (52%), 57% higher than the reference value of 4.9 mg/l (95% confidence interval, 4.14-5.80), mainly caused by higher exposure in children 25-34.9 kg. There were no differences in LPV AUC 0-12h or Ctrough between backbones. CONCLUSION: Children (3-15 years), weighing at least 14 kg and taking LPV/r in second-line treatment achieve adequate exposure of LPV within limits reported to be safe and well tolerated. These data support the use of a LPV/r-based regimen and the adult formulation of 200/50 mg in children 25-34.9 kg.