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Incidence and risk factors for the immune reconstitution inflammatory syndrome in HIV patients in South Africa: a prospective study

Murdoch, David Ma,d; Venter, Willem DFb; Feldman, Charlesc; Van Rie, Anneliesd

doi: 10.1097/QAD.0b013e3282f4a607
Clinical Science

Objective: To determine the incidence, clinical manifestations, risk factors and outcome of immune reconstitution inflammatory syndrome (IRIS) in South Africa.

Design: Prospective surveillance cohort and nested case–control study in a large, University hospital-based antiretroviral therapy (ART) clinic.

Methods: A total of 423 ART-naive HIV-infected South African patients were followed for signs and symptoms IRIS during the first 6 months of ART. We also performed a nested case–control study with controls matched to IRIS cases on ART duration.

Results: During the first 6 months of ART, 44 (10.4%) patients experienced IRIS for an overall incidence rate of 25.1 cases per 100 patient-years. Diagnoses included tuberculosis (18/44, 41%), abscess formation and suppurative folliculitis (8/44, 18.2%), varicella zoster (6/44, 13.6%), herpes simplex (4/44, 9.1%), cryptococcal meningitis (3/44, 6.8%), molluscum contagiosum (3/44, 6.8%), and Kaposi's sarcoma (2/44, 4.5%). Median IRIS onset was 48 days (interquartile range, 29–99) from ART initiation. In comparison with controls, IRIS cases had significantly lower CD4 cell counts at baseline (79 versus 142 cells/μl; P = 0.02) and at IRIS diagnosis (183 versus 263 cells/μl; P = 0.05), but similar virological and immunological response to ART. In multivariable analyses, higher baseline CD4 cell count was protective of developing IRIS (HR 0.72 per 50 cells/μl increase). Most IRIS cases were mild, with ART discontinued in three (6.8%) patients, corticosteroids administered to four (9.1%) patients, and hospitalization required in 12 (27.3%) patients. Two deaths were attributable to IRIS.

Conclusions: IRIS may affect 10% of patients initiating ART in Africa, particularly those with advanced immunosuppression, but severe, life-threatening IRIS is uncommon.

From the aDivision of Pulmonary and Critical Care Medicine, Duke University Medical Center, Durham, North Carolina, USA

bReproductive Health & HIV Research Unit, University of the Witwatersrand, Johannesburg, South Africa

cDivision of Pulmonology, Department of Medicine, Johannesburg Hospital and University of the Witwatersrand, Johannesburg, South Africa

dDepartment of Epidemiology, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.

Received 29 August, 2007

Revised 27 September, 2007

Accepted 3 October, 2007

Correspondence to David M. Murdoch, MD, MPH, Duke University Medical Center, Division of Pulmonary & Critical Care Medicine, DUMC Box 2629, Durham, NC 27710, USA. E-mail:,

© 2008 Lippincott Williams & Wilkins, Inc.