Measuring TB drug levels in the hair in adults and children to monitor drug exposure and outcomes

V. Mave; D. Kadam; S. Gaikwad; A. Kinikar; D. Aguilar; A. Chavan; M. Paradkar; S. V.B. Yogendra; R. Bharadwaj; A. Kagal; N. Suryavanshi; J. Golub; V. Kulkarni; K. E. Dooley; A. Gupta; P. Bacchetti; R. Gerona; N. Gupte; M. Gandhi

doi:10.5588/IJTLD.20.0574

Measuring TB drug levels in the hair in adults and children to monitor drug exposure and outcomes

V. Mave, D. Kadam, S. Gaikwad, A. Kinikar, D. Aguilar, A. Chavan, M. Paradkar, S. V.B. Yogendra, R. Bharadwaj, A. Kagal, N. Suryavanshi, J. Golub, V. Kulkarni, K. E. Dooley, A. Gupta, P. Bacchetti, R. Gerona, N. Gupte, M. Gandhi

School of Medicine

Research output: Contribution to journal › Article › peer-review

2 Scopus citations

Abstract

INTRODUCTION: Testing for anti-TB drugs in small hair samples may serve as a non-invasive tool to measure cumulative drug exposure and/or adherence, as these determine treatment success. We aimed to assess how well hair assays of TB drugs predict TB treatment outcomes. METHODS: A small thatch of hair, ~30 strands, was cut from the occipital region in adults and children from a prospective TB cohort in India. Isoniazid (INH), acetyl-INH and pyrazinamide (PZA) were extracted from the hair samples and quantified using liquid-chromatography-tandem mass spectrometry. The relationship between drug concentrations in hair and time to unfavourable outcomes was assessed using Cox-proportional hazards regression models. RESULTS: A two-fold increase in hair acetyl-INH concentrations in the 264 participants in our cohort with hair assays for TB drugs indicated a lower hazard of unfavourable TB treatment outcomes (aHR 0.67, 95%CI 0.44-1.02) and TB treatment failure (aHR 0.65, 95%CI 0.42-1.01). Higher summed concentrations (a summed measure of INH and acetyl-INH) indicated a lower hazard of treatment failure (aHR 0.69, 95%CI 0.45-1.05) CONCLUSION: Hair levels of INH and its metabolite may predict TB treatment outcomes, indicating the potential utility of this measure to assess and optimise TB treatment outcomes.

Original language	English (US)
Pages (from-to)	52-60
Number of pages	9
Journal	International Journal of Tuberculosis and Lung Disease
Volume	25
Issue number	1
DOIs	https://doi.org/10.5588/IJTLD.20.0574
State	Published - Jan 1 2021

Keywords

Hair assays
Isoniazid hair concentrations
Pyrazinamide hair concentrations
Therapeutic drug monitoring
Tuberculosis

ASJC Scopus subject areas

Pulmonary and Respiratory Medicine
Infectious Diseases

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10.5588/IJTLD.20.0574

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Mave, V., Kadam, D., Gaikwad, S., Kinikar, A., Aguilar, D., Chavan, A., Paradkar, M., Yogendra, S. V. B., Bharadwaj, R., Kagal, A., Suryavanshi, N., Golub, J., Kulkarni, V., Dooley, K. E., Gupta, A., Bacchetti, P., Gerona, R., Gupte, N., & Gandhi, M. (2021). Measuring TB drug levels in the hair in adults and children to monitor drug exposure and outcomes. International Journal of Tuberculosis and Lung Disease, 25(1), 52-60. https://doi.org/10.5588/IJTLD.20.0574

Mave, V, Kadam, D, Gaikwad, S, Kinikar, A, Aguilar, D, Chavan, A, Paradkar, M, Yogendra, SVB, Bharadwaj, R, Kagal, A, Suryavanshi, N, Golub, J, Kulkarni, V, Dooley, KE, Gupta, A, Bacchetti, P, Gerona, R, Gupte, N & Gandhi, M 2021, 'Measuring TB drug levels in the hair in adults and children to monitor drug exposure and outcomes', International Journal of Tuberculosis and Lung Disease, vol. 25, no. 1, pp. 52-60. https://doi.org/10.5588/IJTLD.20.0574

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title = "Measuring TB drug levels in the hair in adults and children to monitor drug exposure and outcomes",

abstract = "INTRODUCTION: Testing for anti-TB drugs in small hair samples may serve as a non-invasive tool to measure cumulative drug exposure and/or adherence, as these determine treatment success. We aimed to assess how well hair assays of TB drugs predict TB treatment outcomes. METHODS: A small thatch of hair, ~30 strands, was cut from the occipital region in adults and children from a prospective TB cohort in India. Isoniazid (INH), acetyl-INH and pyrazinamide (PZA) were extracted from the hair samples and quantified using liquid-chromatography-tandem mass spectrometry. The relationship between drug concentrations in hair and time to unfavourable outcomes was assessed using Cox-proportional hazards regression models. RESULTS: A two-fold increase in hair acetyl-INH concentrations in the 264 participants in our cohort with hair assays for TB drugs indicated a lower hazard of unfavourable TB treatment outcomes (aHR 0.67, 95%CI 0.44-1.02) and TB treatment failure (aHR 0.65, 95%CI 0.42-1.01). Higher summed concentrations (a summed measure of INH and acetyl-INH) indicated a lower hazard of treatment failure (aHR 0.69, 95%CI 0.45-1.05) CONCLUSION: Hair levels of INH and its metabolite may predict TB treatment outcomes, indicating the potential utility of this measure to assess and optimise TB treatment outcomes.",

keywords = "Hair assays, Isoniazid hair concentrations, Pyrazinamide hair concentrations, Therapeutic drug monitoring, Tuberculosis",

author = "V. Mave and D. Kadam and S. Gaikwad and A. Kinikar and D. Aguilar and A. Chavan and M. Paradkar and Yogendra, {S. V.B.} and R. Bharadwaj and A. Kagal and N. Suryavanshi and J. Golub and V. Kulkarni and Dooley, {K. E.} and A. Gupta and P. Bacchetti and R. Gerona and N. Gupte and M. Gandhi",

note = "Funding Information: This work was primarily supported by National Institute of Health/National Institute of Allergy and Infectious Diseases (NIH/ NIAID; Bethesda, MD, USA) (1R21AI127149-01 to VM). Research data in this manuscript were collected, in part, as part of the Regional Prospective Observational Research for Tuberculosis (RePORT) India Consortium. This work was funded in whole or in part by federal funds from the Government of India Department of Biotechnology (DBT); the Indian Council of Medical Research (ICMR; New Delhi, India); the NIH/NIAID Office of AIDS Research; CRDF Global (Arlington, VA, USA); the NIH Baltimore-Washington-India Clinical Trials Unit for NIAID Networks (UM1AI069465 to AG); and the NIH (R01A1I097494 to VM, NG, AG and JEG). Publisher Copyright: {\textcopyright} 2021 The Union",

year = "2021",

month = jan,

day = "1",

doi = "10.5588/IJTLD.20.0574",

language = "English (US)",

volume = "25",

pages = "52--60",

journal = "International Journal of Tuberculosis and Lung Disease",

issn = "1027-3719",

publisher = "International Union against Tubercul. and Lung Dis.",

number = "1",

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TY - JOUR

T1 - Measuring TB drug levels in the hair in adults and children to monitor drug exposure and outcomes

AU - Mave, V.

AU - Kadam, D.

AU - Gaikwad, S.

AU - Kinikar, A.

AU - Aguilar, D.

AU - Chavan, A.

AU - Paradkar, M.

AU - Yogendra, S. V.B.

AU - Bharadwaj, R.

AU - Kagal, A.

AU - Suryavanshi, N.

AU - Golub, J.

AU - Kulkarni, V.

AU - Dooley, K. E.

AU - Gupta, A.

AU - Bacchetti, P.

AU - Gerona, R.

AU - Gupte, N.

AU - Gandhi, M.

N1 - Funding Information: This work was primarily supported by National Institute of Health/National Institute of Allergy and Infectious Diseases (NIH/ NIAID; Bethesda, MD, USA) (1R21AI127149-01 to VM). Research data in this manuscript were collected, in part, as part of the Regional Prospective Observational Research for Tuberculosis (RePORT) India Consortium. This work was funded in whole or in part by federal funds from the Government of India Department of Biotechnology (DBT); the Indian Council of Medical Research (ICMR; New Delhi, India); the NIH/NIAID Office of AIDS Research; CRDF Global (Arlington, VA, USA); the NIH Baltimore-Washington-India Clinical Trials Unit for NIAID Networks (UM1AI069465 to AG); and the NIH (R01A1I097494 to VM, NG, AG and JEG). Publisher Copyright: © 2021 The Union

PY - 2021/1/1

Y1 - 2021/1/1

N2 - INTRODUCTION: Testing for anti-TB drugs in small hair samples may serve as a non-invasive tool to measure cumulative drug exposure and/or adherence, as these determine treatment success. We aimed to assess how well hair assays of TB drugs predict TB treatment outcomes. METHODS: A small thatch of hair, ~30 strands, was cut from the occipital region in adults and children from a prospective TB cohort in India. Isoniazid (INH), acetyl-INH and pyrazinamide (PZA) were extracted from the hair samples and quantified using liquid-chromatography-tandem mass spectrometry. The relationship between drug concentrations in hair and time to unfavourable outcomes was assessed using Cox-proportional hazards regression models. RESULTS: A two-fold increase in hair acetyl-INH concentrations in the 264 participants in our cohort with hair assays for TB drugs indicated a lower hazard of unfavourable TB treatment outcomes (aHR 0.67, 95%CI 0.44-1.02) and TB treatment failure (aHR 0.65, 95%CI 0.42-1.01). Higher summed concentrations (a summed measure of INH and acetyl-INH) indicated a lower hazard of treatment failure (aHR 0.69, 95%CI 0.45-1.05) CONCLUSION: Hair levels of INH and its metabolite may predict TB treatment outcomes, indicating the potential utility of this measure to assess and optimise TB treatment outcomes.

AB - INTRODUCTION: Testing for anti-TB drugs in small hair samples may serve as a non-invasive tool to measure cumulative drug exposure and/or adherence, as these determine treatment success. We aimed to assess how well hair assays of TB drugs predict TB treatment outcomes. METHODS: A small thatch of hair, ~30 strands, was cut from the occipital region in adults and children from a prospective TB cohort in India. Isoniazid (INH), acetyl-INH and pyrazinamide (PZA) were extracted from the hair samples and quantified using liquid-chromatography-tandem mass spectrometry. The relationship between drug concentrations in hair and time to unfavourable outcomes was assessed using Cox-proportional hazards regression models. RESULTS: A two-fold increase in hair acetyl-INH concentrations in the 264 participants in our cohort with hair assays for TB drugs indicated a lower hazard of unfavourable TB treatment outcomes (aHR 0.67, 95%CI 0.44-1.02) and TB treatment failure (aHR 0.65, 95%CI 0.42-1.01). Higher summed concentrations (a summed measure of INH and acetyl-INH) indicated a lower hazard of treatment failure (aHR 0.69, 95%CI 0.45-1.05) CONCLUSION: Hair levels of INH and its metabolite may predict TB treatment outcomes, indicating the potential utility of this measure to assess and optimise TB treatment outcomes.

KW - Hair assays

KW - Isoniazid hair concentrations

KW - Pyrazinamide hair concentrations

KW - Therapeutic drug monitoring

KW - Tuberculosis

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DO - 10.5588/IJTLD.20.0574

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SN - 1027-3719

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JO - International Journal of Tuberculosis and Lung Disease

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Measuring TB drug levels in the hair in adults and children to monitor drug exposure and outcomes

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