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Validation of a published case definition for tuberculosis-associated immune reconstitution inflammatory syndrome
Lewis J Haddow1, Mahomed-Yunus S Moosa, Philippa J Easterbrook
1Division of Immunology, Infection and Inflammatory Disease, King's College London, London, UK. lewis.haddow@kcl.ac.uk
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.
Conclusion:
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.
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