title: Concentration-response model of lopinavir/ritonavir in HIV-1-infected pediatric patients.
abstract: OBJECTIVE
  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.
authors: 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.
authors: Naïm
authors: N
authors: Bouazza
authors: Saik
authors: S
authors: Urien
authors: Stéphane
authors: S
authors: Blanche
authors: Déborah
authors: D
authors: Hirt
authors: Frantz
authors: F
authors: Foissac
authors: Sihem
authors: S
authors: Benaboud
authors: Jean-Marc
authors: JM
authors: Tréluyer
authors: Pierre
authors: P
authors: Frange
mesh_terms: D000293:Adolescent; D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D003198:Computer Simulation; D004305:Dose-Response Relationship, Drug; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism / Q000821:virology; D015497:HIV-1 / Q000302:isolation & purification; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D061466:Lopinavir / Q000008:administration & dosage* / Q000493:pharmacokinetics; D008297:Male; D008954:Models, Biological; D017410:Practice Guidelines as Topic; D012189:Retrospective Studies; D019438:Ritonavir / Q000008:administration & dosage* / Q000493:pharmacokinetics; D019562:Viral Load / Q000187:drug effects
chemical_list: D019380:Anti-HIV Agents; D061466:Lopinavir; D019438:Ritonavir