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.
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.
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.
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.
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.
Accepted for publication January 23, 2014.
J.-M.T. and P.F. contributed equally to this article.
P.F. received grants from French National Agency for Research on AIDS and viral hepatitis (ANRS; to his institution) and from SIDACTION. The authors have no other funding or conflicts of interest to disclose.
Address for correspondence: Naïm Bouazza, PhD, Unité de Recherche Clinique, Hôpital Tarnier, 89 rue d’Assas, 75006 Paris, France. E-mail: firstname.lastname@example.org.