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 moxifloxacincontaining
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.
Additional file 1: Table S1. a. Outcome by treatment within gender
and HIV subgroups. b. Outcome by treatment within gender and smoker
Additional file 2: List of ethics committee approving the REMoxTB