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

Lortholary, Oliviera,c; Fontanet, Arnaudb; Mémain, Nathalied; Martin, Antoinee; Sitbon, Karined; Dromer, Françoisea; for the French Cryptococcosis Study Group

Clinical Science

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.

From the aNational Reference Centre for Mycoses and Antifungals, Molecular Mycology Unit

bEmerging Diseases Epidemiology Unit, Institut Pasteur, Paris

cInfectious and Tropical Diseases Unit, Necker University Hospital, Paris

dInfectious and Tropical Diseases Unit

eHistopathology Unit, Avicenne University Hospital, Bobigny, France.

*See Appendix for study members.

Received 12 January, 2005

Revised 1 February, 2005

Accepted 21 February, 2005

Dr O. Lortholary, National Reference Center for Mycoses and Antifungals, Molecular Mycology Unit, CNRS FRE 2849 Institut Pasteur, 25 rue du Dr Roux, 75724 Paris Cedex 15, France. E-mail: olortho@pasteur.fr

© 2005 Lippincott Williams & Wilkins, Inc.