title: Paradoxical immune reconstitution inflammatory syndrome in HIV-infected patients treated with combination antiretroviral therapy after AIDS-defining opportunistic infection.
abstract: BACKGROUND
  The incidence of immune reconstitution inflammatory syndrome (IRIS) when antiretroviral therapy (ART) is initiated after an AIDS-defining opportunistic infection (OI) is uncertain and understudied for the most common OIs.
  
  
  METHODS
  We examined patients in the University of Washington Human Immunodeficiency Virus Cohort initiating potent ART subsequent to an AIDS-defining OI. IRIS was determined through retrospective medical record review and adjudication using a standardized data collection process and clinical case definition. We compared demographic and clinical characteristics, and immunologic changes in patients with and without IRIS.
  
  
  RESULTS
  Among 196 patients with 260 OIs, 21 (11%; 95% confidence interval, 7%-16%) developed paradoxical IRIS in the first year on ART. The 3 most common OIs among study patients were Pneumocystis pneumonia (PCP, 28%), Candida esophagitis (23%), and Kaposi sarcoma (KS, 16%). Cumulative 1-year incidence of IRIS was 29% (12/41) for KS, 16% (4/25) for tuberculosis, 14% (1/7) for Cryptococcus, 10% (1/10) for Mycobacterium avium complex, and 4% (3/72) for PCP. Morbidity and mortality were highest in those with visceral KS-IRIS compared with other types of IRIS (100% [6/6] vs 7% [1/15], P < .01). Patients with mucocutaneous KS and tuberculosis-IRIS experienced greater median increase in CD4(+) cell count during the first 6 months of ART compared with those without IRIS (+158 vs +53 cells/μL, P = .04, mucocutaneous KS; +261 vs +113, P = .04, tuberculosis).
  
  
  CONCLUSIONS
  Cumulative incidence and features of IRIS varied depending on the OI. IRIS occurred in >10% of patients with KS, tuberculosis, or Cryptococcus. Visceral KS-IRIS led to considerable morbidity and mortality.
authors.affiliation: Department of Medicine, Feinberg School of Medicine, Division of Infectious Diseases and Center for Global Health, Northwestern University, Chicago, Illinois 60611, USA. c-achenbach@northwestern.edu
authors.forename: Chad J
authors.initials: CJ
authors.lastname: Achenbach
authors.forename: Robert D
authors.initials: RD
authors.lastname: Harrington
authors.forename: Shireesha
authors.initials: S
authors.lastname: Dhanireddy
authors.forename: Heidi M
authors.initials: HM
authors.lastname: Crane
authors.forename: Corey
authors.initials: C
authors.lastname: Casper
authors.forename: Mari M
authors.initials: MM
authors.lastname: Kitahata
mesh_terms: D017088:AIDS-Related Opportunistic Infections; D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy*; D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D018414:CD8-Positive T-Lymphocytes; D015331:Cohort Studies; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D054019:Immune Reconstitution Inflammatory Syndrome / Q000139:chemically induced*; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D012189:Retrospective Studies
chemical_list: D019380:Anti-HIV Agents
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