Assessment of tuberculosis disease activity in people infected with Mycobacterium tuberculosis and living with HIV: A longitudinal cohort study
Loading...
Date
2022
Authors
Kroidl, Inge
Ahmed, Mohamed I.M.
Horn, Sacha
Kibuuka, Hannah
Semwogerere, Michael
Mwesigwa, Betty
Naluyima, Prossy
Kasumba, Joy Mary
Maswai, Jonah
Geldmacher, Christof
Journal Title
Journal ISSN
Volume Title
Publisher
EClinicalMedicine
Abstract
Early 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).
Description
Keywords
Incipient tuberculosis, Tuberculosis, Biomarker, HIV
Citation
Kroidl, 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.2022.101470