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Immune reconstitution inflammatory syndrome: incidence and implications for mortality

Novak, Richard M.a; Richardson, James T.b; Buchacz, Katec; Chmiel, Joan S.d; Durham, Marcus D.c; Palella, Frank J.d; Wendrow, Andreaa; Wood, Kathyb; Young, Benjamine,f; Brooks, John T.c; the HIV Outpatient Study (HOPS) Investigators

doi: 10.1097/QAD.0b013e3283511e91
Clinical Science

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.

aUniversity of Illinois, Chicago, Illinois

bCerner Corporation, Vienna, Virginia

cCenters for Disease Control and Prevention (CDC), Atlanta, Georgia

dFeinberg School of Medicine, Northwestern University, Chicago, Illinois

eRocky Mountain CARES/DIDC, Denver, Colorado, USA

fHealth Connections International, Amsterdam, The Netherlands.

Correspondence to Richard M. Novak, MD, Professor of Medicine, University of Illinois, 808 South Wood Street, M/C 735, Chicago, IL 60612, USA. Tel: +1 312 996 6763; fax: +1 312 413 1657; e-mail:

Received 16 July, 2011

Revised 27 December, 2011

Accepted 6 January, 2012

Data presented previously as an abstract at the 5th International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention; July 2009; Cape Town, South Africa.

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© 2012 Lippincott Williams & Wilkins, Inc.