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dc.contributor.authorMurphy, M. E.
dc.contributor.authorWills, G. H.
dc.contributor.authorMurthy, S.
dc.contributor.authorLouw, C.
dc.contributor.authorBateson, A. L. C.
dc.contributor.authorHunt, R. D.
dc.contributor.authorMcHugh, T. D.
dc.contributor.authorNunn, A. J.
dc.contributor.authorMeredith, S. K.
dc.contributor.authorMendel, C. M.
dc.contributor.authorSpigelman, M.
dc.contributor.authorCrook, A. M.
dc.contributor.authorGillespie, S. H.
dc.contributor.authorREMoxTB Consortium
dc.date.accessioned2018-10-17T11:30:11Z
dc.date.available2018-10-17T11:30:11Z
dc.date.issued2018-10-17
dc.identifier.citationMurphy , 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/s12916-018-1169-5en
dc.identifier.issn1741-7015
dc.identifier.otherPURE: 256232732
dc.identifier.otherPURE UUID: 3b8f4d4c-5cde-45f7-897c-bde5ef59c342
dc.identifier.otherRIS: urn:B3D023BF5019E859DF8B353DE2C14E9D
dc.identifier.otherRIS: Murphy2018
dc.identifier.otherScopus: 85054989281
dc.identifier.otherORCID: /0000-0001-6537-7712/work/54819105
dc.identifier.otherWOS: 000447637600001
dc.identifier.urihttps://hdl.handle.net/10023/16255
dc.descriptionThis 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.en
dc.description.abstractBackground: 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.
dc.format.extent11
dc.language.isoeng
dc.relation.ispartofBMC Medicineen
dc.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.en
dc.subjectGenderen
dc.subjectTuberculosisen
dc.subjectTreatment outcomeen
dc.subjectCavitationen
dc.subjectClinical trialsen
dc.subjectREMoxTBen
dc.subjectRA0421 Public health. Hygiene. Preventive Medicineen
dc.subjectE-DASen
dc.subjectSDG 3 - Good Health and Well-beingen
dc.subject.lccRA0421en
dc.titleGender differences in tuberculosis treatment outcomes : a post hoc analysis of the REMoxTB studyen
dc.typeJournal articleen
dc.description.versionPublisher PDFen
dc.contributor.institutionUniversity of St Andrews. School of Medicineen
dc.contributor.institutionUniversity of St Andrews. Infection and Global Health Divisionen
dc.contributor.institutionUniversity of St Andrews. Global Health Implementation Groupen
dc.contributor.institutionUniversity of St Andrews. Gillespie Groupen
dc.contributor.institutionUniversity of St Andrews. Biomedical Sciences Research Complexen
dc.contributor.institutionUniversity of St Andrews. Infection Groupen
dc.identifier.doihttps://doi.org/10.1186/s12916-018-1169-5
dc.description.statusPeer revieweden


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