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

Abstract

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 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.

Conclusions: IRIS-related cryptococcosis was observed more frequently in severely immunocompromised patients with disseminated infection and HAART initiation soon after the diagnosis.