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Pediatric Infectious Disease Journal:
doi: 10.1097/INF.0000000000000298
HIV Reports

Concentration-response Model of Lopinavir/Ritonavir in HIV-1–infected Pediatric Patients

Bouazza, Naïm PhD*†; Urien, Saik MD, PhD*†‡; Blanche, Stéphane MD*‡§; Hirt, Déborah PharmD, PhD*†; Foissac, Frantz PhD*†; Benaboud, Sihem PharmD, PhD*†; Tréluyer, Jean-Marc MD, PhD*†‡¶; Frange, Pierre MD

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Abstract

Objectives:

The aims of this study were to analyze the viral load and CD4+ lymphocyte outcomes and the concentration-response of lopinavir/ritonavir (LPV/r) in the treatment of HIV-1–infected antiretroviral-naive children, to determine whether current dosing guidelines for LPV/r achieve Ctrough above 1.0 mg/L for naive patients to compare efficacy of World Health Organization 2010 and Food and Drug Administration dosing recommendations.

Methods:

Clinical and biologic examinations were performed before treatment, 1 month, 3 months and then every 3 months in 47 antiretroviral-naive children who started an LPV/r-based regimen. LPV concentrations were also monitored on a routine basis, after 2 weeks of treatment initiation, between 1 and 24 hours after dosing in all children. A population pharmacokinetic-pharmacodynamic analysis was performed using an HIV dynamic model. Simulations of World Health Organization 2010 and Food and Drug Administration dosing recommendations were compared in terms of viral suppression.

Results:

The HIV dynamic model adequately described the data. According to the concentration-effect curve, the LPV concentration providing 90% (CLPV90) and 95% (CLPV95) of effect were 1.2 and 2.4 mg/L, respectively. The World Health Organization 2010 guidelines should provide a higher probability of viral success, particularly in infants.

Conclusions:

The CLPV90 derived from this model supports current dosing guidelines. However, the target of 2.4 mg/L corresponding to CLPV95 could be used to enhance the efficacy of this drug in treatment-naive children.

Copyright © 2014 by Lippincott Williams & Wilkins

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