Background: Atazanavir/ritonavir (ATV/r) is a recommended once-daily protease inhibitor. Tenofovir disoproxil fumarate (TDF) can reduce ATV 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 Ctrough below 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.