Jacobs, Tom G.Mumbiro, VivianChitsamatanga, MosesNamuziya, NatashaPassanduca, AlfeuDomínguez Rodríguez, SaraTagarro García, AlfredoNathoo, Kusum J.Nduna, BwendoEMPIRICAL Clinical Trial GroupEt al.2024-02-052024-02-052023Jacobs, 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 (2023). Suboptimal lopinavir exposure in infants on rifampicin treatment receiving double-dosed or semisuperboosted lopinavir/ritonavir: time for a change. JAIDS Journal of Acquired Immune Deficiency Syndromes, 93(1), 42-46. https://doi.org/10.1097/QAI.00000000000031681525-41351077-9450http://hdl.handle.net/11268/12659Background: Although 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 pediatric separate ritonavir formulations needed to superboost. 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 substudy 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 cotreatment, they received double-dosed (ratio 8:2) or semisuperboosted LPV/r (adding a ritonavir 100 mg 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 cotreatment (5 received double-dosed and 4 semisuperboosted LPV/r). The median (IQR) age was 6.4 months (5.4-9.8), weight 6.0 kg (5.2-6.8), and 10/14 were male. Of those receiving rifampicin, 6/9 infants (67%) (67%) had LPV Ctrough ,1.0 mg/L compared with 1/5 (20%) in the control arm. LPV apparent oral clearance was 3.3-fold higher for infants receiving rifampicin. Conclusion: Double-dosed or semisuperboosted 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 coinfection, including twice-daily dolutegravir.engAttribution-NonCommercial-NoDerivatives 4.0 Internacionalhttp://creativecommons.org/licenses/by-nc-nd/4.0/LopinavirRitonavirjournal article10.1097/QAI.0000000000003168open accessPediatríaMedicamentoSida