Assessment of tuberculosis disease activity in people infected with Mycobacterium tuberculosis and living with HIV: A longitudinal cohort study

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dc.contributor.authorKroidl, Inge
dc.contributor.authorAhmed, Mohamed I.M.
dc.contributor.authorHorn, Sacha
dc.contributor.authorKibuuka, Hannah
dc.contributor.authorSemwogerere, Michael
dc.contributor.authorMwesigwa, Betty
dc.contributor.authorNaluyima, Prossy
dc.contributor.authorKasumba, Joy Mary
dc.contributor.authorMaswai, Jonah
dc.contributor.authorGeldmacher, Christof
dc.date.accessioned2022-12-06T11:13:49Z
dc.date.available2022-12-06T11:13:49Z
dc.date.issued2022
dc.description.abstractEarly detection of asymptomatic incipient tuberculosis (TB) could improve clinical outcomes and reduce the spread of Mycobacterium tuberculosis (MTB) infection, particularly in HIV endemic settings. This study assessed TB disease activity over 5 years in people living with HIV co-infected with MTB using a surrogate biomarker. Methods Between Jan 1, 2013 and Aug 31, 2018, 2014 people living with HIV were screened annually for active TB using the Xpert MTB/RIF diagnostic assay in 11 clinics in Kenya, Tanzania, Uganda, and Nigeria. Longitudinal blood mononuclear cell samples from 46 selected patients with active and recurrent tuberculosis, latent infection, or incipient TB were further analysed for MTB-specific T-cell activation (defined by CD38 expression) as a well-defined surrogate marker for TB disease covering a total of 1758 person-months. Findings MTB-specific CD4 T-cell activation differentiated active, Xpert MTB/RIF positive TB from latent TB with a sensitivity and specificity of 86% and was reduced upon TB treatment initiation. Activated MTB-specific T cells were present in 63% and 23% of incipient TB cases 6 and 12 months before diagnosis of active disease, respectively. Transient increases of MTB-specific T cell activation were also observed in individuals with latent infection, while persistent activation was a hallmark of recurrent TB after the end of treatment. Interpretation In most cases, progression to active TB disease started 6−12 months before diagnosis by clinical symptoms and sputum occurrence of bacilli. Blood biomarkers could facilitate early detection of incipient TB, improve clinical outcomes, and reduce the transmission of MTB. Funding This work was supported by the President’s Emergency Plan for AIDS Relief via a cooperative agreement between the Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., and the U.S. Department of Defense [W81XWH-11-2-0174, W81XWH-18-2-0040] and by the Bundesministerium f€ur Bildung und Forschung (BmBF) through funding of the Deutsches Zentrum f€ur Infektionsforschung (DZIF, TTU-TB personalized medicine TTU 02_813).en_US
dc.identifier.citationKroidl, I., Ahmed, M. I., Horn, S., Polyak, C., Esber, A., Parikh, A., ... & Geldmacher, C. (2022). Assessment of tuberculosis disease activity in people infected with Mycobacterium tuberculosis and living with HIV: A longitudinal cohort study. EClinicalMedicine, 49, 101470. https://doi.org/10.1016/j. eclinm.2022.101470en_US
dc.identifier.urihttps://doi.org/10.1016/j. eclinm.2022.101470
dc.identifier.urihttps://nru.uncst.go.ug/handle/123456789/5973
dc.language.isoenen_US
dc.publisherEClinicalMedicineen_US
dc.subjectIncipient tuberculosisen_US
dc.subjectTuberculosisen_US
dc.subjectBiomarkeren_US
dc.subjectHIVen_US
dc.titleAssessment of tuberculosis disease activity in people infected with Mycobacterium tuberculosis and living with HIV: A longitudinal cohort studyen_US
dc.typeArticleen_US
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