Cryptococcal immune reconstitution inflammatory syndrome (IRIS) may present as a clinical worsening or new presentation of cryptococcal disease after initiation of antiretroviral therapy (ART), and is thought to be caused by recovery of cryptococcus-specific immune responses. We have reviewed reports of cryptococcal IRIS and have developed a consensus case definition specifically for paradoxical crytopcoccal IRIS in patients with HIV-1 and known cryptococcal disease before ART, and a separate definition for incident cryptococcosis developed during ART (termed ART-associated cryptococcosis), for which a proportion of cases are likely to be unmasking cryptococcal IRIS. These structured case definitions are intended to aid design of future clinical, epidemiological, and immunopathological studies of cryptococcal IRIS, to standardise diagnostic criteria, and to facilitate comparisons between studies. As for definitions of tuberculosis-associated IRIS, definitions for cryptococcal IRIS should be regarded as preliminary until further insights into the immunopathology of IRIS permit their refinement.
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We acknowledge all participating members of the International Network for the Study of HIV-associated IRIS (INSHI). We thank Mohamed-Yunus Moosa, Tihana Bicanic, Danielle Cohen, Rosalind Parkes-Ratanshi, David Lalloo, David Meya, Andrew Kambugu, and Tom Harrison for discussions and contributions of unpublished data. No specific funding was provided for this work. DRB and PRB receive support from the NIH National Institute of Allergy and Infectious Diseases ( K23AI073192 and R34AI081554-01 , repsectively). SDL and GM are funded by the Wellcome Trust. LJH is funded by the Medical Research Council ( G0700530 ).