by Galileya LT, Wasmann RE, Chabala C, Rabie H, Lee J, Njahira Mukui I, Hesseling A, Zar H, Aarnoutse R, Turkova A, Gibb D, Cotton MF, McIlleron H, Denti P. PLOS Medicine 2023; 20(11): e1004303. doi: 10.1371/journal.pmed.1004303
Summary: Current World Health Organization pediatric tuberculosis dosing guidelines lead to suboptimal drug exposures. The authors of this manuscript pooled data from large pharmacokinetic studies to identify key covariates influencing drug exposure, to optimize tuberculosis dosing in children. Data from 387 children from South Africa, Zambia, Malawi, and India were analysed, of whom 39% were living with HIV (95% on ART). Children older than 3 months have lower rifampicin exposures than adults and increasing their dose by 75 or 150 mg could improve therapy. Altered exposures in children with HIV is probably caused by concomitant ART and not HIV per se. The importance of drug–drug interactions with lopinavir/ritonavir and efavirenz should be evaluated further and considered in future dosing guidance.
