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

Naïm Bouazza1, Saik Urien, Stéphane Blanche

  • 1From 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.

The Pediatric Infectious Disease Journal
|February 11, 2014
PubMed

Insights

This study analyzed lopinavir/ritonavir (LPV/r) dosing in children with HIV-1. Current guidelines support viral suppression, but higher LPV/r targets may improve efficacy in naive pediatric patients.

Area of Science:

  • Pharmacology
  • Virology
  • Pediatrics

Background:

  • Antiretroviral therapy is crucial for managing HIV-1 infection in children.
  • Lopinavir/ritonavir (LPV/r) is a key component in pediatric HIV treatment regimens.
  • Optimizing LPV/r dosing is essential for achieving viral suppression and improving long-term outcomes.

Purpose of the Study:

  • To analyze viral load and CD4+ lymphocyte outcomes with LPV/r in antiretroviral-naive children.
  • To evaluate if current LPV/r dosing guidelines achieve a target trough concentration (Ctrough) above 1.0 mg/L.
  • To compare the efficacy of World Health Organization (WHO) 2010 and Food and Drug Administration (FDA) dosing recommendations.

Main Methods:

  • A population pharmacokinetic-pharmacodynamic analysis using an HIV dynamic model was performed.
  • 47 antiretroviral-naive children receiving LPV/r-based regimens were studied.
  • Simulations compared WHO 2010 and FDA dosing recommendations for viral suppression.

Main Results:

  • The HIV dynamic model accurately described the patient data.
  • The LPV concentration for 90% effect (CLPV90) was 1.2 mg/L, supporting current guidelines.
  • The LPV concentration for 95% effect (CLPV95) was 2.4 mg/L, suggesting a potential for enhanced efficacy.

Conclusions:

  • Current LPV/r dosing guidelines are supported by the CLPV90 derived from the model.
  • A higher target concentration (CLPV95) of 2.4 mg/L could potentially enhance LPV/r efficacy in treatment-naive children.
  • WHO 2010 guidelines appear to offer a higher probability of viral success, especially in infants.
Abstract

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