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 ≥50 copies/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 ≥50 copies/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 (AUC0-24 161 h.mg/l vs. 224 h.mg/l) and lower Clast (1.03 mg/l vs. 5.69 mg/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.