Once vs. twice-daily lopinavir/ritonavir in HIV-1-infected children

Objective:To evaluate whether once daily (q.d.) lopinavir/ritonavir is noninferior to twice daily (b.i.d.) dosing in children.Design:International, multicentre, phase II/III, randomized, open-label, noninferiority trial (KONCERT/PENTA18/ANRS150). Setting:Clinical centres participating in the PENTA, HIV-NAT and PHPT networks.Participants:Children/adolescents with HIV-1 RNA viral load less than 50 copies/ml for at least 24 weeks on lopinavir/ritonavir-containing antiretroviral therapy.Intervention:Children were randomized to continue lopinavir/ritonavir b.i.d. or change to q.d. Main outcome measure:Confirmed viral load 50copies/ml by 48 weeks (12% noninferiority margin). Results:One hundred seventy-three children were randomized in the KONCERT trial (86 q.d., 87 b.i.d.); 46% men, median (IQR) age 11 (9-14) years, CD4% 33 (27-38)%. By week 48, 97 and 98% of time was spent on q.d. and b.i.d., respectively (one q.d. child lost at week 4). Twelve q.d. vs. seven b.i.d. children had confirmed viral load 50copies/ml within 48 weeks; estimated difference in percentage with viral load rebound 6% [90% CI (-2, 14)]. Numbers of children with grade 3/4 adverse events (11 vs. 7) or major resistance mutations (3 vs. 2) were similar, q.d. vs. b.i.d. (both P > 0.3). Among 26 children in an intrasubject lopinavir/ritonavir pharmacokinetic substudy, lower daily exposure (AUC(0-24) 161 h.mg/l vs. 224 h.mg/l) and lower C-last (1.03mg/l vs. 5.69mg/l) were observed with q.d. vs. b.i.d. dosing. Conclusion:Noninferiority for viral load suppression on q.d. vs. b.i.d. lopinavir/ritonavir was not demonstrated. Although results, therefore, do not support routine use of q.d. lopinavir/ritonavir, lack of safety concerns or resistance suggest that q.d. dosing remains an option in selected, adherent children, with close viral load monitoring. Copyright (C) 2015 Wolters Kluwer Health, Inc. All rights reserved.