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The Tuberculosis-Associated Immune Reconstitution Inflammatory Syndrome (TB-IRIS)

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HIV and Tuberculosis

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Abstract

Initiation of antiretroviral therapy (ART) in HIV infected people with tuberculosis (TB) significantly improves their overall prognosis, but paradoxical worsening of the clinical or radiographic manifestations of TB can occur during the initial weeks of ART, a phenomenon that is called immune reconstitution inflammatory syndrome or IRIS. Paradoxical TB-IRIS occurs in patients initiating ART while established on TB treatment and presents with systemic and/or localized symptoms and signs. Patients with more severe CD4 lymphopenia, disseminated TB and more rapid initiation of ART after TB diagnosis are at higher risk. TB-IRIS is thought to represent an aberrant inflammatory response in patients with low CD4 counts and high mycobacterial burden when HIV plasma viremia is suppressed leading to hyperactivation of the innate immune system, especially myeloid cells with inflammasome activation. This triggers exuberant TB-specific CD4 T cell responses and release of proinflammatory cytokines likely resulting in activation of tissue macrophages with production of matrix metalloproteinases contributing to tissue pathology. Apart from drainage of suppurative lesions, treatment with prednisone can alleviate many of the symptoms. Prednisone was also shown to reduce the incidence of paradoxical TB-IRIS in a placebo-controlled clinical trial that enrolled high risk patients with CD4 counts less than 100 cells/μL when starting ART.

The work of IS was supported by the Intramural Research Program of NIAID/NIH.

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Authors and Affiliations

  1. National Institutes of Health, National Institute of Allergy and Infectious Diseases, Bethesda, MD, USA

    Irini Sereti

  2. Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA

    Gregory P. Bisson

  3. Wellcome Centre for Infectious Diseases Research in Africa, Institute of Infectious, Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa

    Graeme Meintjes

  4. Division of Infectious Diseases and HIV Medicine, Department of Medicine, University of Cape Town, Cape Town, South Africa

    Graeme Meintjes

Authors
  1. Irini Sereti
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  2. Gregory P. Bisson
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  3. Graeme Meintjes
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Correspondence to Irini Sereti .

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Editors and Affiliations

  1. National Institute of Health, National Institute of Allergy and Infectious Diseases, Bethesda, MD, USA

    Irini Sereti

  2. Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA

    Gregory P. Bisson

  3. Wellcome Centre for Infectious Diseases Research in Africa, Institute of Infectious Disease and Molecular Medicine, Department of Medicine, University of Cape Town, Division of Infectious Diseases and HIV Medicine, Department of Medicine, University of Cape Town, Cape Town, South Africa

    Graeme Meintjes

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Sereti, I., Bisson, G.P., Meintjes, G. (2019). The Tuberculosis-Associated Immune Reconstitution Inflammatory Syndrome (TB-IRIS). In: Sereti, I., Bisson, G.P., Meintjes, G. (eds) HIV and Tuberculosis. Springer, Cham. https://doi.org/10.1007/978-3-030-29108-2_6

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