Evidence map›Paper›PMID 42477612›Full record

ArticleBMC infectious diseases2026

Exposure to the four first-line anti-tuberculosis drugs and treatment outcomes: a target trial emulation study in Ghana.

Michael Opoku-Mireku, Awewura Kwara, Margaret Y M Lartey, Charles A Peloquin, Divine Aseye Yao Amenuke, Kwasi Adjepong Twum, Priscilla A Nortey, Alexander Ansah Manu, Kwadwo Ansah Koram

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Article in BMC infectious diseases, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

9 authors.

Michael Opoku-MirekuDepartment of Epidemiology and Disease Control, School of Public Health, University of Ghana, Legon, Ghana. mmirekuopoku@gmail.com.ORCID https://orcid.org/0000-0002-1671-1320
Awewura KwaraDepartment of Medicine, University of Florida College of Medicine, Gainesville, FL, USA.
Margaret Y M LarteyDepartment of Medicine, Korle Bu Teaching Hospital, Accra, Ghana.
Charles A PeloquinDepartment of Pharmacotherapy and Translational Research, University of Florida, Gainesville, FL, USA.
Divine Aseye Yao AmenukeDepartment of Medicine, Komfo Anokye Teaching Hospital, Kumasi, Ghana.
Kwasi Adjepong TwumDepartment of Radiology, Komfo Anokye Teaching Hospital, Kumasi, Ghana.
Priscilla A NorteyDepartment of Epidemiology and Disease Control, School of Public Health, University of Ghana, Legon, Ghana.
Alexander Ansah ManuDepartment of Epidemiology and Disease Control, School of Public Health, University of Ghana, Legon, Ghana.
Kwadwo Ansah KoramDepartment of Epidemiology and Disease Control, School of Public Health, University of Ghana, Legon, Ghana.

Funding

Training Program in Tuberculosis and HIV Research in GhanaD43TW010055 · FIC · UNIVERSITY OF FLORIDA · PI KWARA, AWEWURA JACOB · 2015 to 2019
$1.5M
FIC NIH HHS D43 TW010055
6 · The paper itself

Abstract

backgroundTuberculosis (TB) treatment outcomes in sub-Saharan Africa remain suboptimal despite high adherence to first-line therapy. Variability in drug pharmacokinetics, resulting in subtherapeutic plasma concentrations, may contribute to treatment failure and the development of resistance. This study estimated the causal effect of subtherapeutic plasma concentrations of first-line anti-TB drugs on treatment failure or death among individuals with drug-susceptible pulmonary TB in Ghana.

methodsWe conducted a prospective cohort study of 164 adults receiving standard WHO weight-band dosing at five Ghanaian hospitals. Peak plasma concentrations (C

resultsOf 164 participants, 120 had complete pharmacokinetic and outcome data; 20.0% (24/120) had subtherapeutic concentrations of all four drugs. The 6-month risk of treatment failure or death was 33.3% under the low-exposure strategy versus 4.2% under the adequate-exposure strategy (crude RD: 29.1% points). In weighted analyses, low drug exposure was associated with a 23.6%-point increase in absolute risk of treatment failure or death (95% CI: 2.6-44.7; p = 0.028) and a 7-fold higher relative risk (95% CI: 1.83-26.9; p = 0.004), corresponding to approximately one additional poor outcome for every four patients with subtherapeutic levels. Sensitivity analyses were consistent (ATE: 19.9%, 95% CI: 2.3-37.5). The E-value was 15.5 (lower bound 5.0).

conclusionsSubtherapeutic exposure to all four first-line drugs was associated with increased risk of treatment failure or death among patients who survived into the intensive phase. Preventing multidrug subtherapeutic exposure through therapeutic drug monitoring or optimized dosing warrants randomized evaluation in high-burden settings.

trial registrationClinical trial number: not applicable.

Indexed as

GhanaPharmacokineticsSubtherapeutic concentrationsTarget trial emulationTreatment failureTuberculosis

Identifiers

PMID42477612

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