Immune reconstitution inflammatory syndrome: incidence and implications for mortality
Published Date:Mar 27 2012
Corporate Authors:HIV Outpatient Study (HOPS) Investigators
Antiretroviral Therapy, Highly Active
CD4 Lymphocyte Count
Immune Reconstitution Inflammatory Syndrome
Pubmed Central ID:PMC4657750
Funding:200-2001-00133/PHS HHS/United States
CC999999/Intramural CDC HHS/United States
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.
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.
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.
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.
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.
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