title: Cryptococcal immune reconstitution inflammatory syndrome.
abstract: OBJECTIVE
  The epidemiology and pathogenesis of, and risk factors for, cryptococcal immune reconstitution inflammatory syndrome (CM-IRIS) are reviewed with an emphasis on how new insights inform a rational management approach and prevention strategies.
  
  
  RESULTS
  Risk factors for paradoxical CM-IRIS are a low inflammatory response and CD4 cell count at baseline, rapid immune restoration from this low baseline, and a high organism or antigen load at baseline and at antiretroviral therapy (ART) initiation. Detailed immune mechanisms are still unclear. Rapidly fungicidal induction therapy, allowing prompt initiation of ART (from around 3 weeks in resource-limited settings in the context of amphotericin B induction) at a time when organism and antigen loads are low, may reduce overall mortality without exacerbating paradoxical CM-IRIS, compared with initiation of ART at later time points. Recent cohorts suggest early recognition and management can reduce the mortality associated with paradoxical CM-IRIS. Unmasking CM-IRIS is preventable through screening for cryptococcal antigen prior to ART and preemptive antifungal treatment for those testing positive, although prospective studies are needed.
  
  
  CONCLUSIONS
  Optimal antifungal induction and judicious ART timing, together with early recognition and management of developing cases, with thorough exclusion of alternative diagnoses, should help reduce paradoxical CM-IRIS-related mortality. Unmasking CM-IRIS cases should be preventable.
authors.affiliation: Research Centre for Infection and Immunity, Division of Clinical Sciences, St. George's University of London, London, UK.
authors.forename: Nicky
authors.initials: N
authors.lastname: Longley
authors.forename: Thomas S
authors.initials: TS
authors.lastname: Harrison
authors.forename: Joseph N
authors.initials: JN
authors.lastname: Jarvis
mesh_terms: D017088:AIDS-Related Opportunistic Infections / Q000188:drug therapy* / Q000276:immunology / Q000517:prevention & control; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D000935:Antifungal Agents / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D015658:HIV Infections / Q000188:drug therapy; D006801:Humans; D054019:Immune Reconstitution Inflammatory Syndrome / Q000188:drug therapy* / Q000276:immunology / Q000517:prevention & control; D016919:Meningitis, Cryptococcal / Q000175:diagnosis / Q000188:drug therapy* / Q000517:prevention & control; D012307:Risk Factors
chemical_list: D019380:Anti-HIV Agents; D000935:Antifungal Agents