A patient-level pooled analysis of treatment-shortening regimens for drug-susceptible pulmonary tuberculosis


Imperial, MZ, Nahid, P, Phillips, PPJ, Davies, GR ORCID: 0000-0002-3819-490X, Fielding, K, Hanna, D, Hermann, D, Wallis, RS, Johnson, JL, Lienhardt, C et al (show 1 more authors) (2018) A patient-level pooled analysis of treatment-shortening regimens for drug-susceptible pulmonary tuberculosis. Nature Medicine, 24 (11). pp. 1708-1715.

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Abstract

Tuberculosis kills more people than any other infectious disease. Three pivotal trials testing 4-month regimens failed to meet non-inferiority margins; however, approximately four-fifths of participants were cured. Through a pooled analysis of patient-level data with external validation, we identify populations eligible for 4-month treatment, define phenotypes that are hard to treat and evaluate the impact of adherence and dosing strategy on outcomes. In 3,405 participants included in analyses, baseline smear grade of 3+ relative to <2+, HIV seropositivity and adherence of ≤90% were significant risk factors for unfavorable outcome. Four-month regimens were non-inferior in participants with minimal disease defined by <2+ sputum smear grade or non-cavitary disease. A hard-to-treat phenotype, defined by high smear grades and cavitation, may require durations >6 months to cure all. Regimen duration can be selected in order to improve outcomes, providing a stratified medicine approach as an alternative to the ‘one-size-fits-all’ treatment currently used worldwide.

Item Type: Article
Uncontrolled Keywords: anitmicrobial therapy, public health, risk factors, therapeutics, tuberculosis
Depositing User: Symplectic Admin
Date Deposited: 11 Sep 2018 06:43
Last Modified: 19 Jan 2023 01:21
DOI: 10.1038/s41591-018-0224-2
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3026036
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