Terminology and classification

An IRIS is best described in relation to the type of provoking pathogen e.g. tuberculosis-associated IRIS (TB-IRIS) or cryptococcosis-associated IRIS (C-IRIS) because the immunopathogenesis may differ for different types of pathogen. Further classification is based on the body locality or organ involved, e.g. cryptococcal meningitis IRIS (CM-IRIS), or MAC-IRIS lymphadenitis. The temporal relationship between recognition of a pathogen causing an IRIS and ART commencement is also important. Unmasking IRIS is the term used when ART unmasks a previously unrecognised infection whereas paradoxical IRIS is the term used when a previously treated opportunistic infection flares post-ART. For example, unmasking TB-IRIS is diagnosed when an ART-naive patient with no recognisable features of Mycobacterium tuberculosis infection, commences ART and soon after develops tuberculosis (TB). The term ‘ART-associated TB’ is also sometimes used if the TB is not characterised by unusual inflammation. In contrast, paradoxical CM-IRIS is said to occur when an ART-naive HIV patient presents with cryptococcal meningitis (CM), undergoes and displays improvement on CM treatment, then starts ART, after which an exacerbation of CM develops. This detailed classification system helps the clinician predict outcomes and produce a management algorithm. Furthermore, it assists in research on the immunopathogenesis of the various forms of IRIS and the development of strategies for prevention and treatment.