Host Gene Expression Kinetics During Treatment of Tuberculosis in HIV-Coinfected Individuals Is Independent of Highly Active Antiretroviral Therapy

Gebremedhin Gebremicael, Desta Kassa, Edwin Quinten, Yodit Alemayehu, Atsbeha Gebreegziaxier, Yohannes Belay, Debbie van Baarle, Tom H M Ottenhoff, Jacqueline M Cliff*, Mariëlle C Haks

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Background: Limitations in diagnostic tools to discriminate between active tuberculosis and latent Mycobacterium tuberculosis infection and for monitoring antituberculosis treatment responses are major challenges in tuberculosis control, especially in human immunodeficiency virus (HIV)-coinfected individuals.

Methods: Expression levels of 105 immune-related genes were determined in 131 HIV-infected patients with active tuberculosis (n = 48), patients with latent M. tuberculosis infection (LTBI; n = 37), and controls with no M. tuberculosis infection (n = 46) in Addis Ababa, Ethiopia, using focused gene expression profiling with a dual-color reverse-transcription multiplex ligation-dependent probe amplification assay.

Results: Within the cohort of HIV-positive subjects, the expression profiles of 7 genes at baseline (FCGR1A, RAB24, TLR1, TLR4, MMP9, NLRC4, and IL1B) could accurately discriminate between active tuberculosis and both latent and no M. tuberculosis infection, largely independently of (in)eligibility for highly active antiretroviral therapy (HAART). Six months after antituberculosis treatment, biomarker profiles of patients with tuberculosis became indistinguishable from those of patients with LTBI and controls. Importantly, host gene expression kinetics during antituberculosis treatment in HIV-coinfected individuals was found to be independent of HAART use.

Conclusions: Blood transcriptomic profiles can potentially be used as biomarkers to discriminate the different clinical stages of tuberculosis in HIV-coinfected individuals and to monitor tuberculosis treatment responses in both HAART recipients and untreated individuals.

Original languageEnglish
Pages (from-to)1833-1846
Number of pages14
JournalThe Journal of Infectious Diseases
Issue number11
Publication statusPublished - 20-Oct-2018
Externally publishedYes


  • Adult
  • Anti-HIV Agents/therapeutic use
  • Antiretroviral Therapy, Highly Active/statistics & numerical data
  • Biomarkers/analysis
  • Coinfection/genetics
  • Cytokines/analysis
  • Female
  • HIV Infections/complications
  • Humans
  • Longitudinal Studies
  • Male
  • Transcriptome/genetics
  • Tuberculosis/complications
  • Young Adult

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