Jacobs, Tom G; Mumbiro, Vivian; Chitsamatanga, Moses; Namuziya, Natasha; Passanduca, Alfeu; Domínguez-Rodríguez, Sara; Tagarro, Alfredo; Nathoo, Kusum J; Nduna, Bwendo; Ballesteros, Alvaro; +10 more... Madrid, Lola; Mujuru, Hilda A; Chabala, Chishala; Buck, W Chris; Rojo, Pablo; Burger, David M; Moraleda, Cinta; Colbers, Angela; EMPIRICAL Clinical Trial Group; EMPIRICAL Clinical Trial Group; (2023) Brief Report: Suboptimal Lopinavir Exposure in Infants on Rifampicin Treatment Receiving Double-dosed or Semisuperboosted Lopinavir/Ritonavir: Time for a Change. Journal of acquired immune deficiency syndromes, 93 (1). pp. 42-46. ISSN 1525-4135 DOI: https://doi.org/10.1097/QAI.0000000000003168
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Abstract
BACKGROUND: 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%) 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.
Item Type | Article |
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PubMed ID | 36724434 |
Elements ID | 201457 |
Official URL | http://dx.doi.org/10.1097/qai.0000000000003168 |
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Filename: Jacobs-etal-2023-Suboptimal-lopinavir-exposure-in-infants-on-Rifampicin.pdf
Licence: Creative Commons: Attribution-Noncommercial-No Derivative Works 4.0
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