Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, PO Box 30.001, 9700 RB, Groningen, The Netherlands.
Unit of PharmacoTherapy, -Epidemiology and -Economics, Groningen Research Institute of Pharmacy, University of Groningen, Groningen, The Netherlands.
Clin Pharmacokinet. 2019 Jun;58(6):747-766. doi: 10.1007/s40262-018-0716-8.
Contrasting findings have been published regarding the effect of human immunodeficiency virus (HIV) on tuberculosis (TB) drug pharmacokinetics (PK).
The aim of this systematic review was to investigate the effect of HIV infection on the PK of the first-line TB drugs (FLDs) rifampicin, isoniazid, pyrazinamide and ethambutol by assessing all published literature.
Searches were performed in MEDLINE (through PubMed) and EMBASE to find original studies evaluating the effect of HIV infection on the PK of FLDs. The included studies were assessed for bias and clinical relevance. PK data were extracted to provide insight into the difference of FLD PK between HIV-positive and HIV-negative TB patients. This systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement and its protocol was registered at PROSPERO (registration number CRD42017067250).
Overall, 27 studies were eligible for inclusion. The available studies provide a heterogeneous dataset from which consistent results could not be obtained. In both HIV-positive and HIV-negative TB groups, rifampicin (13 of 15) and ethambutol (4 of 8) peak concentration (C) often did not achieve the minimum reference values. More than half of the studies (11 of 20) that included both HIV-positive and HIV-negative TB groups showed statistically significantly altered FLD area under the concentration-time curve and/or C for at least one FLD.
HIV infection may be one of several factors that reduce FLD exposure. We could not make general recommendations with respect to the role of dosing. There is a need for consistent and homogeneous studies to be conducted.
关于人类免疫缺陷病毒（HIV）对结核病（TB）药物药代动力学（PK）的影响，已有相互矛盾的研究结果发表。
本系统评价旨在通过评估所有已发表的文献，研究 HIV 感染对利福平、异烟肼、吡嗪酰胺和乙胺丁醇等一线抗结核药物（FLD）PK 的影响。
在 MEDLINE（通过 PubMed）和 EMBASE 中进行检索，以查找评估 HIV 感染对 FLD PK 影响的原始研究。对纳入的研究进行偏倚和临床相关性评估。提取 PK 数据，以深入了解 HIV 阳性和 HIV 阴性结核病患者 FLD PK 的差异。本系统评价按照系统评价和荟萃分析的首选报告项目进行，并在 PROSPERO（注册号 CRD42017067250）上进行了注册。
总体而言，有 27 项研究符合纳入标准。现有研究提供了一组异质数据集，从中无法得出一致的结果。在 HIV 阳性和 HIV 阴性结核病组中，利福平（15 项研究中的 13 项）和乙胺丁醇（8 项研究中的 4 项）峰值浓度（C）往往未达到最低参考值。包括 HIV 阳性和 HIV 阴性结核病组的半数以上研究（20 项研究中的 11 项）显示至少一种 FLD 的 FLD 浓度-时间曲线下面积和/或 C 的统计学显著改变。
HIV 感染可能是降低 FLD 暴露的因素之一。我们不能对剂量的作用提出一般性建议。需要开展一致和同质的研究。
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