title: Paradoxical reactions and immune reconstitution inflammatory syndrome in tuberculosis.
abstract: The coalescence of the HIV-1 and tuberculosis (TB) epidemics in Sub-Saharan Africa has had a significant and negative impact on global health. The availability of effective antimicrobial treatment for both HIV-1 (in the form of highly active antiretroviral therapy (HAART)) and TB (with antimycobacterial agents) has the potential to mitigate the associated morbidity and mortality. However, the use of both HAART and antimycobacterial therapy is associated with the development of inflammatory paradoxical syndromes after commencement of therapy. These include paradoxical reactions (PR) and immune reconstitution inflammatory syndromes (IRIS), conditions that complicate mycobacterial disease in HIV seronegative and seropositive individuals. Here, we discuss case definitions for PR and IRIS, and explore how advances in identifying the risk factors and immunopathogenesis of these conditions informs our understanding of their shared underlying pathogenesis. We propose that both PR and IRIS are characterized by the triggering of exaggerated inflammation in a setting of immunocompromise and antigen loading, via the reversal of immunosuppression by HAART and/or antimycobacterials. Further understanding of the molecular basis of this pathogenesis may pave the way for effective immunotherapies for the treatment of PR and IRIS.
authors: Division of Infection and Immunity, Cruciform Building, University College London, Gower Street, London WC1E 6BT, UK. Electronic address: lucy.bell.09@ucl.ac.uk.
authors: Lucy C K
authors: LC
authors: Bell
authors: Department of Respiratory Medicine, Guys and St Thomas' NHS Foundation Trust, London, UK.
authors: Ronan
authors: R
authors: Breen
authors: Research Department of Infection and Population Health, Institute of Epidemiology and Healthcare, University College London, London, UK.
authors: Robert F
authors: RF
authors: Miller
authors: Division of Infection and Immunity, Cruciform Building, University College London, Gower Street, London WC1E 6BT, UK.
authors: Mahdad
authors: M
authors: Noursadeghi
authors: Centre for Respiratory Medicine, Royal Free London NHS Foundation Trust, University College London, London, UK.
authors: Marc
authors: M
authors: Lipman
mesh_terms: D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects; D060085:Coinfection / Q000150:complications; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy; D015497:HIV-1; D006801:Humans; D054019:Immune Reconstitution Inflammatory Syndrome / Q000209:etiology* / Q000276:immunology; D008297:Male; D012307:Risk Factors; D014376:Tuberculosis / Q000150:complications* / Q000188:drug therapy
keywords: HIV; IRIS; Immune reconstitution; Mycobacteria; Paradoxical reaction; Tuberculosis