Institutional members access full text with Ovid®

Share this article on:

Pharmacokinetics and Pharmacodynamics of Atazanavir in HIV-1-Infected Children Treated With Atazanavir Powder and Ritonavir: Combined Analysis of the PRINCE-1 and -2 Studies

Sevinsky, Heather*; Zaru, Luna; Wang, Reena; Xu, Xiaohui*; Pikora, Cheryl; Correll, Todd, A.*; Eley, Timothy*

The Pediatric Infectious Disease Journal: December 4, 2017 - Volume Publish Ahead of Print - Issue - p
doi: 10.1097/INF.0000000000001855
HIV Reports: PDF Only

Background: Two clinical studies (PRINCE-1 and -2) in HIV-1-infected children assessed the safety, efficacy, and pharmacokinetics of dual nucleos(t)ide reverse transcriptase inhibitor (NRTI) background therapy plus once-daily atazanavir powder formulation boosted with ritonavir (ATV+RTV). Here, we present a combined analysis of ATV pharmacokinetics and pharmacodynamics across these studies.

Methods: Intensive 24-hour pharmacokinetic profiles at steady state compared ATV exposures (area under the concentration–time curve in one dosing interval [AUCτ]) in 5 ATV+RTV baseline weight-band dosing categories with historic data in adults receiving ATV+RTV 300/100-mg capsules. Repeated ATV Ctrough measurements over 48 weeks explored relationships between ATV composite Ctrough quartiles (CCQs) with virologic efficacy and key safety parameters.

Results: Of 146 children included in this combined analysis, 49.3% were male, 56.8% were Black/African American, and 62.3% were antiretroviral-experienced. Proportions with HIV-1 RNA <50 copies/mL at Week 48 were 13/32, 24/32, 19/32, and 13/28 in the lowest through highest ATV CCQs, respectively. Mean changes from baseline in total bilirubin at Week 48 were +0.3, +0.5, +0.6, and +1.0 mg/dL in the lowest through highest ATV CCQs, respectively. Corresponding proportions with adverse events of hyperbilirubinemia by Week 48 were 1/36, 4/36, 5/36 and 13/35, respectively. Changes from baseline in total amylase or electrocardiogram parameters and adverse events of diarrhea did not vary by ATV CCQs.

Conclusions: Weight-band dosing of ATV+RTV plus optimized dual NRTIs in young HIV-1-infected children achieved similar ATV exposure to that in adults; no unexpected safety findings occurred, and, with the exception of lower virologic suppression in the lowest ATV CCQ, there was no apparent trend in virologic suppression across ATV CCQs.

*Bristol-Myers Squibb, Princeton, New Jersey; Bristol-Myers Squibb, Hopewell, New Jersey; and Bristol-Myers Squibb, Wallingford, Connecticut

Conflicts of Interest and Source of Funding: These studies were supported by Bristol-Myers Squibb, the manufacturer of atazanavir. LZ, RW, XX, and TAC are all employees of and own stock in Bristol-Myers Squibb. HS was an employee of Bristol-Myers Squibb at the time the study was conducted and is now an employee of ViiV Healthcare. CP was an employee of Bristol-Myers Squibb at the time this study was conducted and is now an employee of Gilead Sciences, Inc. TE was an employee of Bristol-Myers Squibb at the time the study was conducted and is now an employee of Arbutus Biopharma Corporation.

ACKNOWLEDGMENTS: The authors would like to thank all study investigators and participants. Medical writing assistance was provided by Julian Martins of inScience Communications, Springer Healthcare, which was funded by Bristol-Myers Squibb.

Address for Correspondence: Todd Correll, PharmD, Bristol-Myers Squibb, Route 206, Province Line Road, Princeton, New Jersey 08543, USA. Tel: (609) 252-7214; Fax: Not available; E-mail:

Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.