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Therapeutics targeting inflammation in the immune reconstitution inflammatory syndrome

  • Lokesh Shahani
    Affiliations
    Section of Infectious Diseases, Department of Medicine, Baylor College of Medicine, Houston, Tex
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  • Richard J. Hamill
    Correspondence
    Reprint requests: Richard J. Hamill, Section of Infectious Diseases (111G), Michael E. DeBakey VA Medical Center, 2002 Holcombe Blvd., Houston, TX 77030-4211
    Affiliations
    Section of Infectious Diseases, Department of Medicine, Baylor College of Medicine, Houston, Tex

    Medical Care Line, Section of Infectious Diseases, Michael E. DeBakey Veterans Affairs Medical Center, Houston, Tex
    Search for articles by this author
Published:August 06, 2015DOI:https://doi.org/10.1016/j.trsl.2015.07.010
      Immune reconstitution inflammatory syndrome (IRIS) is characterized by improvement in a previously incompetent human immune system manifesting as worsening of clinical symptoms secondary to the ability of the immune system to now mount a vigorous inflammatory response. IRIS was first recognized in the setting of human immunodeficiency virus, and this clinical setting continues to be where it is most frequently encountered. Hallmarks of the pathogenesis of IRIS, independent of the clinical presentation and the underlying pathogen, include excessive activation of the immune system, with increased circulating effector memory T cells, and elevated levels of serum cytokines and inflammatory markers. Patients with undiagnosed opportunistic infections remain at risk for unmasking IRIS at the time of active antiretroviral therapy (ART) initiation. Systematic screening for opportunistic infections before starting ART is a key element to prevent this phenomenon. Appropriate management of IRIS requires prompt recognition of the syndrome and exclusion of alternative diagnoses, particularly underlying infections and drug resistance. Controlled studies supporting the use of pharmacologic interventions in IRIS are scare, and recommendations are based on case series and expert opinions. The only controlled trial published to date, showed reduction in morbidity in patients with paradoxical tuberculosis–related IRIS with the use of oral corticosteroids. There are currently limited data to recommend other anti-inflammatory or immunomodulatory therapies that are discussed in this review, and further research is needed. Ongoing research regarding the immune pathogenesis of IRIS will likely direct future rational therapeutic approaches and clinical trials.

      Abbreviations:

      ART (antiretroviral therapy), CCR (chemokine receptor), CI (confidence interval), CMV (Cytomegalovirus), CNS (central nervous system), CRP (C-reactive protein), CSF (cerebrospinal fluid), HIV (human immunodeficiency virus), HR (hazard ratio), IFN (interferon), IP (interferon-γ-inducible protein 10), IL (interleukin), IRIS (immune reconstitution inflammatory syndrome), KS (Kaposi sarcoma), MAC (Mycobacterium avium complex), MHC (major histocompatibility complex), OI (opportunistic infection), OR (odds ratio), PML (progressive multifocal leukoencephalopathy), TB (tuberculosis), Tregs (regulatory T cells), TNF (tumor necrosis factor)
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