A parsimonious host inflammatory biomarker signature predicts incident tuberculosis and mortality in advanced Human Immunodeficiency Virus. Manabe, Y. C, Andrade, B. B, Gupte, N., Leong, S., Kintali, M., Matoga, M., Riviere, C., Samaneka, W., Lama, J. R, Naidoo, K., Zhao, Y., Johnson, W E., Ellner, J. J, Hosseinipour, M. C, Bisson, G. P, Salgame, P., & Gupta, A. Clinical Infectious Diseases, 71(10):2645–2654, Oxford University Press (OUP), dec, 2020.
A parsimonious host inflammatory biomarker signature predicts incident tuberculosis and mortality in advanced Human Immunodeficiency Virus [link]Paper  doi  abstract   bibtex   1 download  
BACKGROUND People with advanced HIV (CD4\textless50) remain at high risk of TB or death despite the initiation of antiretroviral therapy. We aimed to identify immunological profiles that were most predictive of incident TB disease and death. METHOD(S) The REMEMBER randomized clinical trial enrolled 850 participants with HIV (CD4\textless50 cells/micro L) at ART initiation to receive either empiric TB treatment or isoniazid preventive therapy (IPT). A case-cohort study (n=257) stratified by country and treatment arm was performed. Cases were defined as incident TB or all-cause death within 48 weeks after ART initiation. Using multiplexed immunoassay panels and ELISA, 26 biomarkers were assessed in plasma. RESULT(S) 52 (6.1%) of 850 participants developed TB; 47 (5.5%) died (13 of whom had antecedent TB). Biomarkers associated with incident TB overlapped with those associated with death (IL-1beta, IL-6). Biomarker levels declined over time in individuals with incident TB while remaining persistently elevated in those who died. Dividing the cohort into development and validation sets, the final model of 6 biomarkers (CXCL10, IL-1beta, IL-10, sCD14, TNF-alpha, and TNF-beta) achieved a sensitivity of 0.90 (95% CI 0.87-0.94) and a specificity of 0.71(95% CI 0.68-0.75) with an area under the curve (AUC) of 0.81 (95% CI 0.78-0.83) for incident TB. CONCLUSION(S) Among people with advanced HIV, a parsimonious inflammatory biomarker signature predicted those at highest risk for developing TB despite initiation of ART and TB preventive therapies. The signature may be a promising stratification tool to select patients who may benefit from increased monitoring and novel interventions.Copyright The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.
@article{Manabe2020,
abstract = {BACKGROUND People with advanced HIV (CD4{\textless}50) remain at high risk of TB or death despite the initiation of antiretroviral therapy. We aimed to identify immunological profiles that were most predictive of incident TB disease and death. METHOD(S) The REMEMBER randomized clinical trial enrolled 850 participants with HIV (CD4{\textless}50 cells/micro L) at ART initiation to receive either empiric TB treatment or isoniazid preventive therapy (IPT). A case-cohort study (n=257) stratified by country and treatment arm was performed. Cases were defined as incident TB or all-cause death within 48 weeks after ART initiation. Using multiplexed immunoassay panels and ELISA, 26 biomarkers were assessed in plasma. RESULT(S) 52 (6.1{\%}) of 850 participants developed TB; 47 (5.5{\%}) died (13 of whom had antecedent TB). Biomarkers associated with incident TB overlapped with those associated with death (IL-1beta, IL-6). Biomarker levels declined over time in individuals with incident TB while remaining persistently elevated in those who died. Dividing the cohort into development and validation sets, the final model of 6 biomarkers (CXCL10, IL-1beta, IL-10, sCD14, TNF-alpha, and TNF-beta) achieved a sensitivity of 0.90 (95{\%} CI 0.87-0.94) and a specificity of 0.71(95{\%} CI 0.68-0.75) with an area under the curve (AUC) of 0.81 (95{\%} CI 0.78-0.83) for incident TB. CONCLUSION(S) Among people with advanced HIV, a parsimonious inflammatory biomarker signature predicted those at highest risk for developing TB despite initiation of ART and TB preventive therapies. The signature may be a promising stratification tool to select patients who may benefit from increased monitoring and novel interventions.Copyright The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.},
author = {Manabe, Yukari C and Andrade, Bruno B and Gupte, Nikhil and Leong, Samantha and Kintali, Manisha and Matoga, Mitch and Riviere, Cynthia and Samaneka, Wadzanai and Lama, Javier R and Naidoo, Kogieleum and Zhao, Yue and Johnson, W Evan and Ellner, Jerrold J and Hosseinipour, Mina C and Bisson, Gregory P and Salgame, Padmini and Gupta, Amita},
doi = {10.1093/cid/ciz1147},
file = {:C$\backslash$:/Users/01462563/AppData/Local/Mendeley Ltd./Mendeley Desktop/Downloaded/Manabe et al. - 2020 - A parsimonious host inflammatory biomarker signature predicts incident tuberculosis and mortality in advanced Hum.pdf:pdf},
issn = {1058-4838},
journal = {Clinical Infectious Diseases},
keywords = {biological markers,fund{\_}not{\_}ack,hiv,inflammatory markers,mortality,original,plasma,tuberculosis},
mendeley-tags = {fund{\_}not{\_}ack,original},
month = {dec},
number = {10},
pages = {2645--2654},
pmid = {31761933},
publisher = {Oxford University Press (OUP)},
title = {{A parsimonious host inflammatory biomarker signature predicts incident tuberculosis and mortality in advanced Human Immunodeficiency Virus}},
url = {https://academic.oup.com/cid/article/71/10/2645/5639757},
volume = {71},
year = {2020}
}
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