Pharmacokinetics of Atazanavir/ritonavir among HIV-infected Thai children concomitantly taking tenofovir disoproxil fumarate

Abstract

Copyright © 2014 by Lippincott Williams and Wilkins. Background: Atazanavir/ritonavir (ATV/r) is a recommended once-daily protease inhibitor. Tenofovir disoproxil fumarate (TDF) can reduce AT V exposure. The authors studied ATV pharmacokinetic (PK) parameters among children who received atazanavir/ritonavir co-administered with TDF. Methods: HIV-infected children aged 6-18 years with a body weight of 25-50 kg were eligible. Branded ATV 200 mg/capsule was taken with generic ritonavir 100 mg/tablet once daily plus TDF and lamivudine. A 24-hour PK study was performed at week 4 at t = 0 (pre-dose), 2, 4, 6, 8, 10, 12 and 24 hours. PK parameters were calculated using non-compartmental methods with WinNonlin software. Targeted ATV AUC0-24 was 15 mg h/L and Ctrough was 0.15 mg/L. Comparisons of geometric means of ATV PK parameters between different weight bands were made using regression models. Results: Eighteen HIV-infected children with a median (IQR) age of 13 (11-14) years were enrolled. Median (range) body weight and body surface area were 35 (25-42) kg and 1.21 (0.96-1.35) m2, respectively. Median (IQR) CD4 cell count was 735 (540-1233) cells/mm3. Median (range) of ATV was 164 (145-209) mg/m2. Geometric mean (SD) ATV AUC0-24 was 35.05 (1.06) mg h/L, and ATV Ctrough was 0.31 (1.13) mg/L. No child had ATV AUC0-24 or Ctroughbelow target levels. There were no significant differences in PK parameters among weight bands. Conclusion: Atazanavir/ritonavir 200/100 mg dosing provided adequate ATV AUC0-24 when used with TDF in HIV-infected Thai children weighing between 25 and 50 kg.