Jacobs, T. G., Mumbiro, V., Chitsamatanga, M., Namuziya, N., Passanduca, A., Domínguez-Rodríguez, S., Tagarro, A., Nathoo, K. J., Nduna, B., Ballesteros, A., Madrid, L., Mujuru, H. A., Chabala, C., Buck, W. C., Rojo, P., Burger, D. M., Moraleda, C., Colbers, A., & EMPIRICAL Clinical Trial Group
, Journal of acquired immune deficiency syndromes (1999), 10.1097/QAI.0000000000003168. Advance online publication. https://doi.org/10.1097/QAI.0000000000003168
Journal of acquired immune deficiency syndromes
Background: While super-boosted lopinavir/ritonavir (LPV/r; ratio 4:4 instead of 4:1) is recommended for infants living with HIV and receiving concomitant rifampicin, in clinical practice many different LPV/r dosing strategies are applied due to poor availability of paediatric separate ritonavir formulations needed to super-boost. We evaluated LPV pharmacokinetics in infants with HIV receiving LPV/r dosed according to local guidelines in various sub-Saharan African countries with or without rifampicin-based tuberculosis (TB)-treatment.
Methods: This was a 2-arm pharmacokinetic sub-study nested within the EMPIRICAL trial (#NCT03915366). Infants aged 1-12 months recruited into the main study were administered LPV/r according to local guidelines and drug availability either with or without rifampicin-based TB-treatment; during rifampicin co-treatment they received double-dosed (ratio 8:2) or semi-superboosted LPV/r (adding a ritonavir 100mg crushed tablet to the evening LPV/r dose). Six blood samples were taken over 12 hours after intake of LPV/r.
Results: In total, 14/16 included infants had evaluable pharmacokinetic curves; 9/14 had rifampicin co-treatment (5 received double-dosed and 4 semi-superboosted LPV/r). The median (IQR) age was 6.4 months (5.4-9.8), weight 6.0kg (5.2-6.8) and 10/14 were male. Of those receiving rifampicin, 6/9 (67%) infants had LPV C trough <1.0mg/L compared to 1/5 (20%) in the control arm. LPV apparent oral clearance was 3.3-fold higher for infants receiving rifampicin.
Conclusion: Double-dosed or semi-superboosted LPV/r for infants aged 1-12 months receiving rifampicin resulted in substantial proportions of subtherapeutic LPV levels. There is an urgent need for data on alternative antiretroviral regimens in infants with HIV/TB co-infection, including twice-daily dolutegravir.