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Tytuł:
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A Parsimonious Host Inflammatory Biomarker Signature Predicts Incident Tuberculosis and Mortality in Advanced Human Immunodeficiency Virus.
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Autorzy:
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Manabe YC; Division of Infectious Diseases, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Andrade BB; Instituto Gonçalo Moniz, Fundação Oswaldo Cruz (FIOCRUZ), Salvador, Bahia, Brazil.; Multinational Organization Network Sponsoring Translational and Epidemiological Research (MONSTER), José Silveira Foundation, Salvador, Bahia, Brazil.; Wellcome Centre for Infectious Disease Research in Africa, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa.
Gupte N; Division of Infectious Diseases, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.; Byramjee-Jeejeebhoy Government Medical College Johns Hopkins University Clinical Research Site, Pune, India.
Leong S; Department of Medicine, Center for Emerging Pathogens, Rutgers, New Jersey Medical School, Newark, New Jersey, USA.
Kintali M; Department of Medicine, Center for Emerging Pathogens, Rutgers, New Jersey Medical School, Newark, New Jersey, USA.
Matoga M; University of North Carolina Project Malawi, Lilongwe, Malawi.
Riviere C; Les Centres GHESKIO Clinical Research Site, Port au Prince, Haiti.
Samaneka W; University of Zimbabwe College of Health Sciences, Clinical Trials Research Centre, Harare, Zimbabwe.
Lama JR; Asociacion Civil Impacta Salud y Educacion, Lima, Peru.
Naidoo K; Centre for the AIDS Programme of Research in South Africa (CAPRISA), University of KwaZulu-Natal, Durban, South Africa.; CAPRISA-MRC Human Immunodeficiency Virus - Tuberculosis Pathogenesis and Treatment Research Unit, Doris Duke Medical Research Institute, University of KwaZulu-Natal, Durban, South Africa.
Zhao Y; Department of Medicine, Boston Medical Center, Boston, Massachusetts, USA.
Johnson WE; Department of Medicine, Boston Medical Center, Boston, Massachusetts, USA.
Ellner JJ; Department of Medicine, Center for Emerging Pathogens, Rutgers, New Jersey Medical School, Newark, New Jersey, USA.
Hosseinipour MC; University of North Carolina Project Malawi, Lilongwe, Malawi.; Department of Medicine, Division of Infectious Diseases, University of North Carolina School of Medicine, Chapel Hill, North Carolina, USA.
Bisson GP; Division of Infectious Diseases, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Salgame P; Department of Medicine, Center for Emerging Pathogens, Rutgers, New Jersey Medical School, Newark, New Jersey, USA.
Gupta A; Division of Infectious Diseases, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
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Źródło:
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Clinical infectious diseases : an official publication of the Infectious Diseases Society of America [Clin Infect Dis] 2020 Dec 17; Vol. 71 (10), pp. 2645-2654.
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Typ publikacji:
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Journal Article; Randomized Controlled Trial; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
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Język:
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English
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Imprint Name(s):
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Publication: Jan. 2011- : Oxford : Oxford University Press
Original Publication: Chicago, IL : The University of Chicago Press, c1992-
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MeSH Terms:
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HIV Infections*/complications
HIV Infections*/drug therapy
Tuberculosis*/diagnosis
Tuberculosis*/drug therapy
Tuberculosis*/epidemiology
Antitubercular Agents/therapeutic use ; Biomarkers ; CD4 Lymphocyte Count ; Cohort Studies ; HIV ; Humans
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Grant Information:
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D43 TW009771 United States TW FIC NIH HHS; UM1 AI068634 United States AI NIAID NIH HHS; UM1 AI069469 United States AI NIAID NIH HHS; UM1 AI069465 United States AI NIAID NIH HHS; UM1 AI106701 United States AI NIAID NIH HHS; U01 AI115940 United States AI NIAID NIH HHS; U01 AI068634 United States AI NIAID NIH HHS; UM1 AI068636 United States AI NIAID NIH HHS
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Contributed Indexing:
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Keywords: antiretroviral therapy; biomarker; early mortality; tuberculosis
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Molecular Sequence:
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ClinicalTrials.gov NCT01380080
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Substance Nomenclature:
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0 (Antitubercular Agents)
0 (Biomarkers)
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Entry Date(s):
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Date Created: 20191126 Date Completed: 20210428 Latest Revision: 20210929
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Update Code:
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20240104
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PubMed Central ID:
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PMC7744990
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DOI:
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10.1093/cid/ciz1147
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PMID:
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31761933
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Background: People with advanced human immunodeficiency virus (HIV) (CD4 < 50) remain at high risk of tuberculosis (TB) or death despite the initiation of antiretroviral therapy (ART). We aimed to identify immunological profiles that were most predictive of incident TB disease and death.
Methods: The REMEMBER randomized clinical trial enrolled 850 participants with HIV (CD4 < 50 cells/µL) 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.
Results: In total, 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 (interleukin [IL]-1β, 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-1β, IL-10, sCD14, tumor necrosis factor [TNF]-α, and TNF-β) achieved a sensitivity of 0.90 (95% confidence interval [CI]: .87-.94) and a specificity of 0.71(95% CI: .68-.75) with an area under the curve (AUC) of 0.81 (95% CI: .78-.83) for incident TB.
Conclusion: 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.
Clinical Trials Registration: NCT01380080.
(© 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.)
