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. 2023 Apr;163(4):778-789.
doi: 10.1016/j.chest.2022.09.024. Epub 2022 Sep 26.

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

Sona Deshmukh  1 , Manasi Sane  1 , Sanjay Gaikwad  2 , Tushar Sahasrabudhe  3 , Madhusudan Barthwal  3 , Rahul Lokhande  2 , Swapnil Raskar  1 , Anju Kagal  2 , Sujata Dharmshale  2 , Neeta Pradhan  1 , Akshay Gupte  4 , Omamah Alfarisi  4 , Amita Gupta  4 , Kelly E Dooley  4 , Nikhil Gupte  5 , Jonathan E Golub  3 , Vidya Mave  6
Affiliations

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

Sona Deshmukh et al. Chest. 2023 Apr.

Abstract

Background: The role of sex differences in clinical presentation, TB drug pharmacokinetic variables, and treatment outcomes is unclear.

Research question: What is the effect of sex on TB disease severity, drug exposure, and treatment outcome?

Study design and methods: 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.

Results: 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 < 7 days) 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.

Interpretation: 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.

Keywords: TB treatment outcomes; clinical presentation; drug exposure; mycobacterial burden; sex.

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Figures

Figure 1
Figure 1
The estimated effect of sex on TB clinical presentation (A) and on TB treatment outcomes (B) in Pune, India. A, *Adjusted for age (linear), education, BMI (linear), HBA1c (linear), HIV. B, *Unfavorable composite outcome = composite outcome includes treatment failure, recurrence and all-cause mortality; **Measures of association (ratio) unfavorable composite outcomes and TB treatment failure: incidence risk ratio; Recurrence and all-cause mortality, 2-month culture conversion, 1-month culture conversion, time to culture conversion: hazard ratio; ***Adjusted for age (linear), education, BMI (linear), HBA1c (linear). TTD = time to TB detection.
Figure 2
Figure 2
Kaplan-Meier curve showing time to culture conversion (A) and time to all-cause mortality (B) according to sex in Pune, India. ATT = anti-TB treatment.
Figure 3
Figure 3
Sex-wise proportion of participants above the therapeutic target concentration in the enrolled cohort, Pune, India. INH = isoniazid; PZA = pyrazinamide; RMP = rifampin.
e-Figure 1
e-Figure 1
See this image and copyright information in PMC

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