Rifampicin exposure in tuberculosis patients with comorbidities in sub-Saharan Africa: prioritising populations for treatment—a systematic review and meta-analysis
File(s)
Published version
Author(s)
Type
Journal Article
Abstract
Background and Objectives
Emerging evidence suggests that comorbidities like human immunodeficiency virus (HIV) infection, diabetes mellitus (DM), and malnutrition in tuberculosis (TB) patients can alter drug concentrations, thereby affecting the treatment outcomes. For these populations, personalised strategies such as therapeutic drug monitoring (TDM) may be essential. We investigated the variations of drug levels within comorbid populations and analysed the differences in patterns observed between sub-Saharan Africa (SSA) and non-SSA regions.
Methods
We performed a systematic review and meta-analysis of rifampicin drug pharmacokinetics (PK) through searches of major databases from 1980 to December 2023. A random-effects meta-analysis model using R-studio version 4.3.2 was conducted to estimate pooled serum rifampicin exposure (area under the concentration-time curve [AUC], and peak maximum concentration [Cmax]) between patients with TB-HIV infection, and TB-DM.
Results
From 3300 articles screened, 24 studies met inclusion criteria, contributing 33 comorbidity subgroups for meta-analysis. In SSA, 14 subgroups assessed rifampicin PK in TB-HIV, 1 in TB-DM, and none in TB-malnutrition. The pooled mean Cmax was below the recommended range (8–24 mg/L) for all subgroups. For TB-HIV, the pooled Cmax was 5.59 mg/L, 95% CI (4.59–6.59), I2 = 97% for SSA populations and 5.59 mg/L, 95% CI (3.65; 6.59) for non-SSA populations. The Cmax for TB-DM in SSA (9.60 ± 4.4 mg/L) exceeded non-SSA (4.27 mg/L, 95% CI [2.77–5.76]). The lowest AUC was in TB-HIV (SSA, 29.09 mg/L h, 95% CI [21.06; 37.13, I2 = 91%]). High variability and heterogeneity (I2 >90%) were observed, with most studies (20/23) showing low bias.
Conclusion
Our results emphasise the need for individualised dosing and targeted TDM implementation among TB-HIV and TB-DM populations on rifampicin in SSA. Although all populations exhibited low Cmax levels, TB-HIV populations may be prioritised as AUC levels were lowest. In clinical settings in SSA, Cmax-based TDM is more practical, but AUC can be used in treatment where feasible.
Emerging evidence suggests that comorbidities like human immunodeficiency virus (HIV) infection, diabetes mellitus (DM), and malnutrition in tuberculosis (TB) patients can alter drug concentrations, thereby affecting the treatment outcomes. For these populations, personalised strategies such as therapeutic drug monitoring (TDM) may be essential. We investigated the variations of drug levels within comorbid populations and analysed the differences in patterns observed between sub-Saharan Africa (SSA) and non-SSA regions.
Methods
We performed a systematic review and meta-analysis of rifampicin drug pharmacokinetics (PK) through searches of major databases from 1980 to December 2023. A random-effects meta-analysis model using R-studio version 4.3.2 was conducted to estimate pooled serum rifampicin exposure (area under the concentration-time curve [AUC], and peak maximum concentration [Cmax]) between patients with TB-HIV infection, and TB-DM.
Results
From 3300 articles screened, 24 studies met inclusion criteria, contributing 33 comorbidity subgroups for meta-analysis. In SSA, 14 subgroups assessed rifampicin PK in TB-HIV, 1 in TB-DM, and none in TB-malnutrition. The pooled mean Cmax was below the recommended range (8–24 mg/L) for all subgroups. For TB-HIV, the pooled Cmax was 5.59 mg/L, 95% CI (4.59–6.59), I2 = 97% for SSA populations and 5.59 mg/L, 95% CI (3.65; 6.59) for non-SSA populations. The Cmax for TB-DM in SSA (9.60 ± 4.4 mg/L) exceeded non-SSA (4.27 mg/L, 95% CI [2.77–5.76]). The lowest AUC was in TB-HIV (SSA, 29.09 mg/L h, 95% CI [21.06; 37.13, I2 = 91%]). High variability and heterogeneity (I2 >90%) were observed, with most studies (20/23) showing low bias.
Conclusion
Our results emphasise the need for individualised dosing and targeted TDM implementation among TB-HIV and TB-DM populations on rifampicin in SSA. Although all populations exhibited low Cmax levels, TB-HIV populations may be prioritised as AUC levels were lowest. In clinical settings in SSA, Cmax-based TDM is more practical, but AUC can be used in treatment where feasible.
Date Issued
2025-08
Date Acceptance
2025-05-25
Citation
Clinical Pharmacokinetics, 2025, 64 (8), pp.1149-1163
ISSN
0312-5963
Publisher
Springer Science and Business Media LLC
Start Page
1149
End Page
1163
Journal / Book Title
Clinical Pharmacokinetics
Volume
64
Issue
8
Copyright Statement
© The Author(s) 2025 Open Access This article is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License, which permits any non-commercial use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc/4.0/.
License URL
Identifier
10.1007/s40262-025-01537-w
Publication Status
Published
Date Publish Online
2025-07-03