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.
From the *HIV-NAT, the Thai Red Cross AIDS Research Centre; †Division of Infectious Disease, Department of Pediatrics, Ramathibodi Hospital, Mahidol University; ‡SEARCH, the Thai Red Cross AIDS Research Centre; §Department of Internal Medicine, and ¶Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
The study was presented as an oral abstract at the Asian Congress of Pediatric Infectious Diseases, Sri Lanka, November 28–December 1, 2012.
This study was supported by TREAT Asia/amfAR, The Foundation for AIDS Research, with support from the ViiV Healthcare Paediatric Innovation Seed Fund; the Thai National Health Security Office for antiretrovirals and certain laboratory testing; and The Thai Government Pharmaceutical Organization (GPO) for ritonavir 100 mg tablets. Dr. Puthanakit was funded in part as a Senior Researcher Scholar through the Thai Research Fund (TRF). The content of this publication is solely the responsibility of the authors and does not necessarily represent the official views of any of the institutions mentioned above.
All participating sites received institutional review board approval for the study.
All authors declare no conflict of interest and that members of their immediate families do not have a financial interest in or arrangement with any commercial organization that may have a direct interest in the subject matter of this article.
Address for correspondence: Thanyawee Puthanakit, MD, HIV-NAT, the Thai Red Cross AIDS Research Centre, 104 Ratchadamri Road, Pathumwan, Bangkok 10330, Thailand. E-mail: email@example.com