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Gender differences in tuberculosis treatment outcomes : a post hoc analysis of the REMoxTB study

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Date
17/10/2018
Author
Murphy, M. E.
Wills, G. H.
Murthy, S.
Louw, C.
Bateson, A. L. C.
Hunt, R. D.
McHugh, T. D.
Nunn, A. J.
Meredith, S. K.
Mendel, C. M.
Spigelman, M.
Crook, A. M.
Gillespie, S. H.
REMoxTB Consortium
Keywords
Gender
Tuberculosis
Treatment outcome
Cavitation
Clinical trials
REMoxTB
RA0421 Public health. Hygiene. Preventive Medicine
E-DAS
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Abstract
Background: In the REMoxTB study of 4-month treatment-shortening regimens containing moxifloxacin compared to the standard 6-month regimen for tuberculosis, the proportion of unfavourable outcomes for women was similar in all study arms, but men had more frequent unfavourable outcomes (bacteriologically or clinically defined failure or relapse within 18 months after randomisation) on the shortened moxifloxacin-containing regimens. The reason for this gender disparity in treatment outcome is poorly understood. Methods: The gender differences in baseline variables were calculated, as was time to smear and culture conversion and Kaplan-Meier plots were constructed. In post hoc exploratory analyses, multivariable logistic regression modelling and an observed case analysis were used to explore factors associated with both gender and unfavourable treatment outcome. Results: The per-protocol population included 472/1548 (30%) women. Women were younger and had lower rates of cavitation, smoking and weight (all p < 0.05) and higher prevalence of HIV (10% vs 6%, p = 0.001). They received higher doses (mg/kg) than men of rifampicin, isoniazid, pyrazinamide and moxifloxacin (p ≤ 0.005). There was no difference in baseline smear grading or mycobacterial growth indicator tube (MGIT) time to positivity. Women converted to negative cultures more quickly than men on Lowenstein-Jensen (HR 1.14, p = 0.008) and MGIT media (HR 1.19, p < 0.001). In men, the presence of cavitation, positive HIV status, higher age, lower BMI and ‘ever smoked’ were independently associated with unfavourable treatment outcome. In women, only ‘ever smoked’ was independently associated with unfavourable treatment outcome. Only for cavitation was there a gender difference in treatment outcomes by regimen; their outcome in the 4-month arms was significantly poorer compared to the 6-month treatment arm (p < 0.001). Women, with or without cavities, and men without cavities had a similar outcome on all treatment arms (p = 0.218, 0.224 and 0.689 respectively). For all other covariate subgroups, there were no differences in treatment effects for men or women. Conclusions: Gender differences in TB treatment responses for the shorter regimens in the REMoxTB study may be explained by poor outcomes in men with cavitation on the moxifloxacin-containing regimens. We observed that women with cavities, or without, on the 4-month moxifloxacin regimens had similar outcomes to all patients on the standard 6-month treatment. The biological reasons for this difference are poorly understood and require further exploration.
Citation
Murphy , M E , Wills , G H , Murthy , S , Louw , C , Bateson , A L C , Hunt , R D , McHugh , T D , Nunn , A J , Meredith , S K , Mendel , C M , Spigelman , M , Crook , A M , Gillespie , S H & REMoxTB Consortium 2018 , ' Gender differences in tuberculosis treatment outcomes : a post hoc analysis of the REMoxTB study ' , BMC Medicine , vol. 16 , 189 . https://doi.org/10.1186/s12916-018-1169-5
Publication
BMC Medicine
Status
Peer reviewed
DOI
https://doi.org/10.1186/s12916-018-1169-5
ISSN
1741-7015
Type
Journal article
Rights
© The Author(s). 2018 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted 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. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
Description
This study was supported by the Global Alliance for TB Drug Development with support from the Bill and Melinda Gates Foundation, the European and Developing Countries Clinical Trials Partnership (grant IP.2007.32011.011), US Agency for International Development, UK Department for International Development, Directorate General for International Cooperation of the Netherlands, Irish Aid, Australia Department of Foreign Affairs and Trade and National Institutes of Health, AIDS Clinical Trials Group and by grants from the National Institute of Allergy and Infectious Diseases (NIAID) (UM1AI068634, UM1 AI068636 and UM1AI106701) and by NIAID grants to the University of KwaZulu Natal, South Africa, AIDS Clinical Trials Group (ACTG) site 31422 (1U01AI069469); to the Perinatal HIV Research Unit, Chris Hani Baragwanath Hospital, South Africa, ACTG site 12301 (1U01AI069453); and to the Durban International Clinical Trials Unit, South Africa, ACTG site 11201 (1U01AI069426); Bayer Healthcare for the donation of moxifloxacin and Sanofi for the donation of rifampin.
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  • University of St Andrews Research
URI
http://hdl.handle.net/10023/16255

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