Immune reconstitution inflammatory syndrome: Incidence and implications for mortality

Richard M. Novak*, James T. Richardson, Kate Buchacz, Joan S. Chmiel, Marcus D. Durham, Frank J. Palella, Andrea Wendrow, Kathy Wood, Benjamin Young, John T. Brooks, Rose K. Baker, Darlene Hankerson, Carl Armon, Carolyn Studney, Onyinye Enyia, Kenneth A. Lichtenstein, Cheryl Stewart, John Hammer, Kenneth S. Greenberg, Barbara WidickJoslyn D. Axinn, Bienvenido G. Yangco, Kalliope Halkias, Douglas J. Ward, Jay Miller, Jack Fuhrer, Linda Ording-Bauer, Rita Kelly, Jane Esteves, Ellen M. Tedaldi, Ramona A. Christian, Faye Ruley, Dania Beadle

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

72 Scopus citations


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. DESIGN: 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 log10 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 log10 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 log10 copies vs. less than 4.0 log10 copies (OR 2.3). IRIS with a type B-defining or type C-defining diagnosis approximately doubled the risk for all-cause mortality. CONCLUSION: 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.

Original languageEnglish (US)
Pages (from-to)721-730
Number of pages10
Issue number6
StatePublished - Mar 27 2012


  • HIV
  • United States
  • immune reconstitution inflammatory syndrome
  • mortality
  • opportunistic infections
  • risk factors

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases


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