title: 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.
  
  
  METHODS
  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.
authors.affiliation: National Reference Centre for Mycoses and Antifungals, Molecular Mycology Unit bEmerging Diseases Epidemiology Unit, Institut Pasteur, Paris, France. olortho@pasteur.fr
authors.forename: Olivier
authors.initials: O
authors.lastname: Lortholary
authors.forename: Arnaud
authors.initials: A
authors.lastname: Fontanet
authors.forename: Nathalie
authors.initials: N
authors.lastname: Mémain
authors.forename: Antoine
authors.initials: A
authors.lastname: Martin
authors.forename: Karine
authors.initials: K
authors.lastname: Sitbon
authors.forename: Françoise
authors.initials: F
authors.lastname: Dromer
mesh_terms: D017088:AIDS-Related Opportunistic Infections / Q000139:chemically induced*; D000328:Adult; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects*; D003422:Critical Care; D003453:Cryptococcosis / Q000139:chemically induced* / Q000276:immunology; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D007108:Immune Tolerance / Q000187:drug effects*; D015994:Incidence; D007249:Inflammation / Q000139:chemically induced*; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D012307:Risk Factors; D013577:Syndrome
chemical_list: D000893:Anti-Inflammatory Agents