Lopinavir–ritonavir super-boosting in young HIV-infected children on rifampicin-based tuberculosis therapy compared with lopinavir–ritonavir without rifampicin: a pharmacokinetic modelling and clinical study

This study is registered with ClinicalTrials.gov, number NCT02348177.FindingsBetween Jan 30, 2013, and Nov 9, 2015, 96 children with a median age of 18·2 months (IQR 9·6–26·8) were enrolled. Of these 96 children, 80 (83%) completed the first three pharmacokinetic evaluations. Tuberculosis therapy was started before antiretrovirals in 70 (73%) children. The model-predicted percentage of morning Cmin of less than 1·0 mg/L after tuberculosis treatment without super-boosting was 8·8% (95% CI 0·6–19·8) versus 7·6% (0·4–16·2) during super-boosting and tuberculosis treatment. The difference of −1·1% (95% CI −6·9 to 3·2), at a non-inferiority margin of 10%, confirmed the non-inferiority of lopinavir trough concentrations during rifampicin co-treatment. 19 serious adverse events were reported in 12 participants. Three deaths and a temporary treatment interruption due to jaundice were unrelated to study treatment.InterpretationLopinavir exposure with ritonavir super-boosting in a one-to-one ratio during rifampicin-based tuberculosis treatment was non-inferior to the exposure with lopinavir–ritonavir without rifampicin. Safe and effective, field application of super-boosting is limited by poor acceptability. Access to better adapted solid formulations will most likely facilitate public health implementation of this strategy.FundingDNDi, French Development Agency, UBS Optimus Foundation, and Unitaid.
Source: The Lancet HIV - Category: Infectious Diseases Source Type: research