Sex Differences in TB Clinical Presentation, Drug Exposure, and Treatment Outcomes in India

Abstract

The role of sex differences in clinical presentation, TB drug pharmacokinetic variables, and treatment outcomes is unclear. What is the effect of sex on TB disease severity, drug exposure, and treatment outcome? This study was a prospective cohort study conducted in India. It assessed TB disease severity; risk of unfavorable treatment outcomes (failure, recurrence, and death) according to sex; and risk factors for unfavorable outcomes stratified according to sex. Effects of sex on the pharmacokinetic variables (maximum concentration and area under the curve) of rifampicin, isoniazid, and pyrazinamide were estimated by using noncompartmental analyses. Of 1,541 people with microbiologically confirmed TB, 567 (37%) were women. Women had a lower risk of high mycobacterial burden (smear grade≥ 2 and/or time to detection< 7days) with an adjusted OR of 0.70 (95%CI, 0.56-0.87). Among the 744 participants who were followed up prospectively, 261 (35%) were women. Women had a lower risk of unfavorable treatment outcomes (adjusted incidence risk ratio, 0.60; 95%CI, 0.43-0.85), mostly because recurrence was lower (adjusted incidence risk ratio, 0.45; 95%CI, 0.23-0.86). Isoniazid (but not rifampicin and pyrazinamide) maximum concentration and area under the curve were significantly higher among women (P< .01) than men. Among women, unfavorable outcomes were more likely among those with cavitary disease, but among men, increased risk of unfavorable outcomes was associated with alcohol use, higher BMI, and lower glycated hemoglobin level. Women present with lower mycobacterial burden, achieve higher TB drug exposure, and are less likely to have unfavorable treatment outcomes than men. Strategies to improve TB treatment success should take into account sex differences in risk factors for unfavorable outcomes.