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Tuberculosis Immune Reconstitution Inflammatory Syndrome in Children Initiating Antiretroviral Therapy for HIV Infection: A Systematic Literature Review

Link-Gelles, Ruth MPH*; Moultrie, Harry MB ChB, MSc; Sawry, Shobna MSc; Murdoch, David MD, MPH; Van Rie, Annelies MD, PhD*

The Pediatric Infectious Disease Journal: May 2014 - Volume 33 - Issue 5 - p 499–503
doi: 10.1097/INF.0000000000000142
HIV Reports

Background: People with HIV initiating combination antiretroviral therapy are at risk for tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS). While this syndrome has been well researched in adults, little is known about the incidence, case fatality, underlying immunopathology and treatment approaches in children.

Methods: Major databases were searched for articles related to TB-IRIS in children. Data were abstracted using standardized forms.

Results: Thirteen studies were identified: 6 retrospective and 2 prospective cohort studies, 1 cross-sectional study, 3 case reports and 1 case series. In total, 303 cases of TB-IRIS were described, of which 270 were unmasking TB-IRIS, 12 paradoxical TB-IRIS and 21 were not classifiable due to lack of key information. None of the cohort studies had investigation of TB-IRIS as its primary aim. Nine studies were from Africa, 3 from Asia and 1 from Latin America. Age at cART initiation (reported by 12 studies) ranged from 1 month to 16 years. Median time from start of cART to IRIS diagnosis (reported by 8 studies) ranged from 8 days to 16 weeks. Few deaths attributable to TB-IRIS were recorded. Treatment was only discussed in 2 case studies, both of which reported children receiving corticosteroids. No studies evaluated risk factors for, or immunopathogenesis of, pediatric TB-IRIS.

Conclusions: There is a paucity of information available on TB-IRIS in children. Future research assessing incidence, risk factors, case fatality and optimal treatment or prevention strategies of TB-IRIS is needed.

Supplemental Digital Content is available in the text.

From the *Department of Epidemiology, University of North Carolina, Chapel Hill, NC; Wits Reproductive Health and HIV Institute, University of the Witwatersrand, Johannesburg, South Africa; and Duke University Medical Center, Durham, NC.

Accepted for publication October 11, 2013.

Funding for this study was granted by the US National Institute of Health Award 1 R01 HD058972-01. This research was supported by the University of North Carolina at Chapel Hill Center for AIDS Research, an National Institute of Health funded program P30 AI50410. The authors have no other funding or conflicts of interest to disclose.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (

Address for correspondence: Ruth Link-Gelles, MPH, Department of Epidemiology, The University of North Carolina at Chapel Hill, McGravan-Greenberg Hall, CB #7435, Chapel Hill, NC 27599. E-mail:

© 2014 by Lippincott Williams & Wilkins, Inc.