A systematic review on the effect of HIV infection on the pharmacokinetics of first-line tuberculosis drugs
File(s)
Published version
Author(s)
Type
Journal Article
Abstract
Introduction
Contrasting findings have been published regarding the effect of human immunodeficiency virus (HIV) on tuberculosis (TB) drug pharmacokinetics (PK).
Objectives
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.
Methods
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).
Results
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 (Cmax) 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 Cmax for at least one FLD.
Conclusions
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.
Contrasting findings have been published regarding the effect of human immunodeficiency virus (HIV) on tuberculosis (TB) drug pharmacokinetics (PK).
Objectives
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.
Methods
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).
Results
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 (Cmax) 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 Cmax for at least one FLD.
Conclusions
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.
Date Issued
2019-06-01
Date Acceptance
2018-09-07
Citation
Clinical Pharmacokinetics, 2019, 58 (6), pp.747-766
ISSN
1179-1926
Publisher
Springer Verlag
Start Page
747
End Page
766
Journal / Book Title
Clinical Pharmacokinetics
Volume
58
Issue
6
Copyright Statement
© The Author(s) 2018. This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/), which permits any noncommercial use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
Sponsor
Wellcome Trust
Wellcome Trust
Grant Number
097816/Z/11/ZR
104803/Z/14/Z
Subjects
Science & Technology
Life Sciences & Biomedicine
Pharmacology & Pharmacy
ANTI-TB DRUGS
ANTITUBERCULOSIS DRUGS
ISONIAZID PHARMACOKINETICS
CLINICAL PHARMACOKINETICS
PULMONARY TUBERCULOSIS
TREATMENT OUTCOMES
RIFAMPIN
PYRAZINAMIDE
ETHAMBUTOL
CHILDREN
1115 Pharmacology and Pharmaceutical Sciences
Pharmacology & Pharmacy
Publication Status
Published
Date Publish Online
2018-11-08