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

Abstract

Immune reconstitution inflammatory syndrome (IRIS) in association with cryptococcosis has been anecdotically reported following administration of highly active antiretroviral therapy (HAART). To analyse the incidence and risk factors for IRIS-associated cryptococcosis among HIV-infected patients. Retrospective multicentre study between 1996 and 2000 through the French Cryptococcosis Database. Subsequent occurrence of IRIS examined in 120 HIV-infected adult patients treated with HAART and experiencing a first episode of culture-confirmed cryptococcosis. 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 x 10 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. IRIS-related cryptococcosis was observed more frequently in severely immunocompromised patients with disseminated infection and HAART initiation soon after the diagnosis.