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BMC Med. 2018 Oct 17;16(1):189. doi: 10.1186/s12916-018-1169-5.

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

Author information

1
UCL Centre for Clinical Microbiology, Division of Infection and Immunity, University College London, Royal Free Campus, Rowland Hill Street, London, NW3 2PF, England, UK. michael.murphy@ucl.ac.uk.
2
MRC Clinical Trials Unit at UCL, Institute for Clinical Trials and Methodology, Aviation House, 125 Kingsway, London, WC2B 6NH, England, UK.
3
UCL Centre for Clinical Microbiology, Division of Infection and Immunity, University College London, Royal Free Campus, Rowland Hill Street, London, NW3 2PF, England, UK.
4
Madibeng Centre for Research, Brits, South Africa.
5
Department of Family Medicine, School of medicine, University of Pretoria, Pretoria, South Africa.
6
Global Alliance for Tuberculosis Drug Development, New York, NY, 10005, USA.
7
School of Medicine, Medical and Biological Sciences Building, University of St Andrews, North Haugh, St Andrews, KY16 9TF, Scotland, UK.

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.

KEYWORDS:

Cavitation; Clinical trials; Gender; REMoxTB; Treatment outcome; Tuberculosis

PMID:
30326959
PMCID:
PMC6192317
DOI:
10.1186/s12916-018-1169-5
[Indexed for MEDLINE]
Free PMC Article

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