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

Inge Kroidl; Mohamed I M Ahmed; Sacha Horn; Christina Polyak; Allahna Esber; Ajay Parikh; Leigh Anne Eller; Hannah Kibuuka; Michael Semwogerere; Betty Mwesigwa; Prossy Naluyima; Joy Mary Kasumba; Jonah Maswai; John Owuoth; Valentine Sing'oei; Eric Rono; Rebecca Loose; Michael Hoelscher; Julie Ake; Christof Geldmacher; AFRICOS Study Group

doi:10.1016/j.eclinm.2022.101470

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

EClinicalMedicine. 2022 Jul 13:49:101470. doi: 10.1016/j.eclinm.2022.101470. eCollection 2022 Jul.

Authors

Inge Kroidl^{1

2}, Mohamed I M Ahmed^{1

2}, Sacha Horn¹, Christina Polyak^{3

4}, Allahna Esber^{3

4}, Ajay Parikh^{3

4}, Leigh Anne Eller^{3

4}, Hannah Kibuuka⁵, Michael Semwogerere⁵, Betty Mwesigwa⁵, Prossy Naluyima⁵, Joy Mary Kasumba⁵, Jonah Maswai^{3

6}, John Owuoth^{7

8}, Valentine Sing'oei^{7

8}, Eric Rono^{7

8}, Rebecca Loose¹, Michael Hoelscher^{1

2}, Julie Ake³, Christof Geldmacher^{1

2}; AFRICOS Study Group

Affiliations

¹ Division of Infectious Diseases and Tropical Medicine, University Hospital of Munich (LMU), Munich, Germany.
² German Center for Infection Research (DZIF), partner site Munich, Munich, Germany.
³ U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
⁴ Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, MD, USA.
⁵ Makerere University Walter Reed Project, Kampala, Uganda.
⁶ HJF Medical Research International, Kericho, Kenya.
⁷ U.S. Army Medical Research Directorate - Africa, Kisumu, Kenya.
⁸ HJF Medical Research International, Kisumu, Kenya.

Abstract

Background: 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 für Bildung und Forschung (BmBF) through funding of the Deutsches Zentrum für Infektionsforschung (DZIF, TTU-TB personalized medicine TTU 02_813).

Keywords: Biomarker; HIV; Incipient tuberculosis; Tuberculosis.