Abstract

Introduction

Management of concomitant use of ART and TB drugs is difficult because of the many drug–drug interactions (DDIs) between the medications. This systematic review provides an overview of the current state of knowledge about the pharmacokinetics (PK) of ART and TB treatment in children with HIV/TB co-infection, and identifies knowledge gaps.

Methods

We searched Embase and PubMed, and systematically searched abstract books of relevant conferences, following PRISMA guidelines. Studies not reporting PK parameters, investigating medicines that are not available any longer or not including children with HIV/TB co-infection were excluded. All studies were assessed for quality.

Results

In total, 47 studies met the inclusion criteria. No dose adjustments are necessary for efavirenz during concomitant first-line TB treatment use, but intersubject PK variability was high, especially in children <3 years of age. Super-boosted lopinavir/ritonavir (ratio 1:1) resulted in adequate lopinavir trough concentrations during rifampicin co-administration. Double-dosed raltegravir can be given with rifampicin in children >4 weeks old as well as twice-daily dolutegravir (instead of once daily) in children older than 6 years. Exposure to some TB drugs (ethambutol and rifampicin) was reduced in the setting of HIV infection, regardless of ART use. Only limited PK data of second-line TB drugs with ART in children who are HIV infected have been published.

Conclusions

Whereas integrase inhibitors seem favourable in older children, there are limited options for ART in young children (<3 years) receiving rifampicin-based TB therapy. The PK of TB drugs in HIV-infected children warrants further research.

中文翻译：

---

HIV / TB合并感染儿童抗逆转录病毒和肺结核药物的药代动力学：系统评价

摘要

介绍

由于药物之间存在许多药物相互作用，因此难以同时使用抗逆转录病毒药物和抗结核药物。这项系统的综述概述了艾滋病毒/结核病合并感染儿童的抗病毒治疗和抗结核药物的药代动力学（PK）的当前知识状态，并确定了知识差距。

方法

我们搜索了Embase和PubMed，并按照PRISMA指南系统搜索了相关会议的摘要。排除了未报告PK参数，不再提供或未包括HIV / TB合并感染儿童的研究药物的研究。所有研究均经过质量评估。

结果

总共有47项研究符合纳入标准。依法韦仑在同时进行一线结核治疗时无需调整剂量，但受试者间PK变异性较高，尤其是在3岁以下的儿童中。在利福平共同给药期间，超级增强的洛匹那韦/利托那韦（比率1：1）可导致足够的洛匹那韦谷浓度。大于4周龄的儿童可与利福平同时服用双倍的raltegravir，对于6岁以上的儿童，可每日服用两次dolutegravir（而不是每天一次）。无论是否使用抗逆转录病毒疗法，在HIV感染的情况下，减少了对某些结核病药物（乙胺丁醇和利福平）的接触。在感染艾滋病毒的儿童中，只有二线结核病抗病毒药物的PK数据有限。

结论

整合酶抑制剂似乎对年长的儿童有利，而接受基于利福平的结核病治疗的年幼儿童（<3岁）的抗逆转录病毒疗法选择有限。艾滋病毒感染儿童中结核病药物的PK有待进一步研究。