Naïm Bouazza1, Saik Urien, Stéphane Blanche, Déborah Hirt, Frantz Foissac, Sihem Benaboud, Jean-Marc Tréluyer, Pierre Frange. 1. From the *EA 3620, Université Paris Descartes, Sorbonne Paris Cité; †Unité de Recherche Clinique, Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Tarnier; ‡CIC-0901 Inserm, Cochin-Necker; §Unité d'Immunologie, Hématologie et Rhumatologie Pédiatriques, AP-HP, Hôpital Necker Enfants Malades, Paris; ¶Service de Pharmacologie Clinique, AP-HP, Hôpital Cochin-Saint-Vincent-de-Paul, Université Paris-Descartes, Sorbonne Paris Cité, France.
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.
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.
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