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Incidence and risk factors of immune reconstitution inflammatory syndrome complicating HIV-associated cryptococcosis in France

Background:Immune reconstitution inflammatory syndrome (IRIS) in association with cryptococcosis has been anecdotically reported following administration of highly active antiretroviral therapy (HAART). Objective:To analyse the incidence and risk factors for IRIS-associated cryptococcosis among HIV-infected patients. Design:Retrospective multicentre study between 1996 and 2000 through the French Cryptococcosis Database. Methods:Subsequent occurrence of IRIS examined in 120 HIV-infected adult patients treated with HAART and experiencing a first episode of culture-confirmed cryptococcosis. Results:Ten patients developed IRIS during the study period, giving an incidence of 10/239, or 4.2/100 person-years [95% confidence interval (CI), 2.2–7.8]. IRIS consisted of acute symptoms consistent with inflammation occurring within a median of 8 months (range, 2–37) after the diagnosis of cryptococcosis in the context of negative cultures and immunological and/or virological response to HAART. Radiology and histopathology detected features compatible with inflammation. Symptom severity required transfer into intensive care units for three patients and use of anti-inflammatory drugs for four. Three patients with evolutive IRIS died. Compared with patients without IRIS for whom complete clinical and microbiological information were available at baseline, previously unknown HIV infection [odds ratio (OR), 4.8; 95% CI, 1.0–21.7], CD4 cell count < 7 × 106 cells/l (OR, 4.0; 95% CI, 0.9–17.2), fungaemia (OR, 6.1; 95% CI, 1.1–35.2) and HAART initiation within 2 months of cryptococcosis diagnosis (OR, 5.50; 95% CI, 1.0–29.6) were independently associated with the risk of subsequent IRIS. Conclusions:IRIS-related cryptococcosis was observed more frequently in severely immunocompromised patients with disseminated infection and HAART initiation soon after the diagnosis.