title: Immune reconstitution inflammatory syndrome:  incidence and implications for mortality.
abstract: OBJECTIVE
  To describe incidence of immune reconstitution inflammatory syndrome (IRIS) and its association with mortality in a large multisite US HIV-infected cohort applying an objective, comprehensive definition.
  
  
  METHODS
  We studied 2,610 patients seen during 1996-2007 who initiated or resumed highly active combination antiretroviral therapy (cART) and, during the next 6 months, demonstrated a decline in plasma HIV-RNA viral load of at least 0.5 log(10) copies/ml or an increase of at least 50% in CD4 cell count per microliter. We defined IRIS as the diagnosis of a type B or C condition [as per the Centers for Disease Control and Prevention (CDC) 1993 AIDS case definition] or any new mucocutaneous disorder during this same 6-month period.
  
  
  METHODS
  We assessed the incidence of IRIS and evaluated risk factors for IRIS using conditional logistic regression and for all-cause mortality using proportional hazards models.
  
  
  RESULTS
  We identified 370 cases of IRIS (in 276 patients). Median and nadir CD4 cell counts at cART initiation were 90 and 43 cells/μl, respectively; median viral load was 2.7 log(10) copies/ml. The most common IRIS-defining diagnoses were candidiasis (all forms), cytomegalovirus infection, disseminated Mycobacterium avium intracellulare, Pneumocystis pneumonia, varicella zoster, Kaposi's sarcoma and non-Hodgkin lymphoma. Only one case of Mycobacterium tuberculosis was observed. IRIS was independently associated with CD4 cell count less than 50 cells/μl vs. at least 200 cells/μl [odds ratio (OR) 5.0] and a viral load of at least 5.0 log(10) copies vs. less than 4.0 log(10) copies (OR 2.3). IRIS with a type B-defining or type C-defining diagnosis approximately doubled the risk for all-cause mortality.
  
  
  CONCLUSIONS
  In this large US-based HIV-infected cohort, IRIS occurred in 10.6% of patients who responded to effective ART and contributed to increased mortality.
authors.affiliation: University of Illinois, Chicago, 60612, USA. rmnovak@uic.edu
authors.forename: Richard M
authors.initials: RM
authors.lastname: Novak
authors.forename: James T
authors.initials: JT
authors.lastname: Richardson
authors.forename: Kate
authors.initials: K
authors.lastname: Buchacz
authors.forename: Joan S
authors.initials: JS
authors.lastname: Chmiel
authors.forename: Marcus D
authors.initials: MD
authors.lastname: Durham
authors.forename: Frank J
authors.initials: FJ
authors.lastname: Palella
authors.forename: Andrea
authors.initials: A
authors.lastname: Wendrow
authors.forename: Kathy
authors.initials: K
authors.lastname: Wood
authors.forename: Benjamin
authors.initials: B
authors.lastname: Young
authors.forename: John T
authors.initials: JT
authors.lastname: Brooks
mesh_terms: D000293:Adolescent; D000328:Adult; D023241:Antiretroviral Therapy, Highly Active / Q000401:mortality*; D001424:Bacterial Infections / Q000401:mortality*; D018791:CD4 Lymphocyte Count; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology / Q000401:mortality*; D006801:Humans; D054019:Immune Reconstitution Inflammatory Syndrome / Q000401:mortality*; D015994:Incidence; D008297:Male; D008875:Middle Aged; D012367:RNA, Viral; D012307:Risk Factors; D014481:United States / Q000453:epidemiology; D019562:Viral Load; D055815:Young Adult
chemical_list: D012367:RNA, Viral