Pharmacokinetic data of atazanavir/ritonavir in second-line treatment of children living with HIV.

Background: There are limited data on the pharmacokinetics of atazanavir/ritonavir (ATV/r) in children living with HIV, and no data when combined with emtricitabine/tenofovir alafenamide. Here were present the results of an intensive pharmacokinetic sub-study nested within the CHAPAS-4 trial (ISRCTN22964075), to evaluate ATV/r exposure in children.

Methods: Children aged 3 - 15 years, weighing 14 - 24.9 kg received 200/75 mg of ATV/r once daily; those weighing ≥25 kg received 300/100 mg of ATV/r once daily. ATV/r was used in combination with either emtricitabine/tenofovir alafenamide or standard-of-care backbone (abacavir/lamivudine or zidovudine/lamivudine). At steady state, blood samples were taken pre-dose and at 1, 2, 4, 6, 8, 12, and 24 hours after drug intake to construct pharmacokinetic curves. Pharmacokinetic parameters were compared to published values of approved ATV/r adult dosing.

Results: We enrolled 54 children. For ATV/r, the geometric mean (GM) area under the concentration time curve (AUC0-24h) was 44.3 h*mg/L (coefficient of variation [CV%], 47%), which is comparable to adults taking ATV/r 300/100 mg once daily). The GM trough concentration (Ctrough) was 0.48 mg/L (70%), which is 25% lower than the adults reference value of 0.64 mg/L (97%). Nonetheless, all individual Ctrough values were above the target of 0.14 mg/L.

Conclusions: This nested pharmacokinetic sub-study shows that children weighing 14-24.9 kg and >25 kg taking ATV/r 200/75 mg and 300/100 mg respectively, achieve concentrations comparable to those that are safe and effective in adults.