title: Validation of a published case definition for tuberculosis-associated immune reconstitution inflammatory syndrome.
abstract: OBJECTIVE
  To evaluate the International Network for the Study of HIV-associated IRIS (INSHI) case definitions for tuberculosis (TB)-associated immune reconstitution inflammatory syndrome (IRIS) in a South African cohort.
  
  
  METHODS
  Prospective cohort of 498 adult HIV-infected patients initiating antiretroviral therapy. Patients were followed up for 24 weeks and all clinical events were recorded. Events with TB-IRIS as possible cause were assessed by consensus expert opinion and INSHI case definition. Positive, negative, and chance-corrected agreement (kappa) were calculated, and reasons for disagreement were assessed.
  
  
  RESULTS
  One hundred and two (20%) patients were receiving TB therapy at antiretroviral therapy initiation. Three hundred and thirty-three events were evaluated (74 potential paradoxical IRIS, 259 potential unmasking IRIS). Based on expert opinion, there were 18 cases of paradoxical IRIS associated with TB and/or other opportunistic disease. The INSHI criteria for TB-IRIS agreed in 13 paradoxical cases, giving positive agreement of 72.2%, negative agreement in 52/56 non-TB-IRIS events (92.9%), and kappa of 0.66. There were 19 unmasking TB-IRIS cases based on expert opinion, of which 12 were considered IRIS using the INSHI definition (positive agreement 63.2%). There was agreement in all 240 non-TB-IRIS events (negative agreement 100%) and kappa was 0.76.
  
  
  CONCLUSIONS
  There was good agreement between the INSHI case definition for both paradoxical and unmasking TB-IRIS and consensus expert opinion. These results support the use of this definition in clinical and research practice, with minor caveats in its application.
authors.affiliation: Division of Immunology, Infection and Inflammatory Disease, King's College London, London, UK. lewis.haddow@kcl.ac.uk
authors.forename: Lewis J
authors.initials: LJ
authors.lastname: Haddow
authors.forename: Mahomed-Yunus S
authors.initials: MY
authors.lastname: Moosa
authors.forename: Philippa J
authors.initials: PJ
authors.lastname: Easterbrook
mesh_terms: D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D032921:Consensus; D005260:Female; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy / Q000453:epidemiology; D006801:Humans; D054019:Immune Reconstitution Inflammatory Syndrome / Q000453:epidemiology*; D008297:Male; D011446:Prospective Studies; D014376:Tuberculosis / Q000150:complications* / Q000188:drug therapy / Q000453:epidemiology