TY - JOUR
T1 - Sex Differences in TB Clinical Presentation, Drug Exposure, and Treatment Outcomes in India
AU - Deshmukh, Sona
AU - Sane, Manasi
AU - Gaikwad, Sanjay
AU - Sahasrabudhe, Tushar
AU - Barthwal, Madhusudan
AU - Lokhande, Rahul
AU - Raskar, Swapnil
AU - Kagal, Anju
AU - Dharmshale, Sujata
AU - Pradhan, Neeta
AU - Gupte, Akshay
AU - Alfarisi, Omamah
AU - Gupta, Amita
AU - Dooley, Kelly Elise
AU - Gupte, Nikhil
AU - Golub, Jonathan E.
AU - Mave, Vidya
N1 - Funding Information:
This work was supported by the NIH [NIH 1R01A1I097494 to J. E. G.] and by the National Institute of Allergy and Infectious Diseases of the NIH [UM1AI069465]. Data in this article were also collected as part of the Regional Prospective Observational Research for Tuberculosis (RePORT) India Consortium under CRDF Global Agreement #OISE-15-614381-1 and #DAA3-18-64774-1. This project has been funded in whole or in part with federal funds from the Government of India’s Department of Biotechnology, the Indian Council of Medical Research, the NIH, the National Institute of Allergy and Infectious Diseases, and the Office of AIDS Research, and was distributed in part by CRDF Global. The authors also acknowledge support from Persistent Systems in kind.
Publisher Copyright:
© 2022 American College of Chest Physicians
PY - 2023/4
Y1 - 2023/4
N2 - 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.
AB - 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.
KW - TB treatment outcomes
KW - clinical presentation
KW - drug exposure
KW - mycobacterial burden
KW - sex
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U2 - 10.1016/j.chest.2022.09.024
DO - 10.1016/j.chest.2022.09.024
M3 - Article
C2 - 36174745
AN - SCOPUS:85147118198
SN - 0012-3692
VL - 163
SP - 778
EP - 789
JO - CHEST
JF - CHEST
IS - 4
ER -