Concentration-response model of lopinavir/ritonavir in HIV-1-infected pediatric patients

Pediatr Infect Dis J. 2014 Aug;33(8):e213-8. doi: 10.1097/INF.0000000000000298.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Anti-HIV Agents / administration & dosage*
  • Anti-HIV Agents / pharmacokinetics
  • CD4-Positive T-Lymphocytes / drug effects
  • CD4-Positive T-Lymphocytes / immunology
  • Child
  • Child, Preschool
  • Computer Simulation
  • Dose-Response Relationship, Drug
  • Female
  • HIV Infections / drug therapy*
  • HIV Infections / immunology
  • HIV Infections / metabolism
  • HIV Infections / virology
  • HIV-1 / isolation & purification
  • Humans
  • Infant
  • Infant, Newborn
  • Lopinavir / administration & dosage*
  • Lopinavir / pharmacokinetics
  • Male
  • Models, Biological*
  • Practice Guidelines as Topic
  • Retrospective Studies
  • Ritonavir / administration & dosage*
  • Ritonavir / pharmacokinetics
  • Viral Load / drug effects


  • Anti-HIV Agents
  • Lopinavir
  • Ritonavir