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Incidence, Spectrum and Outcome of Immune Reconstitution Syndrome in HIV-infected Children after Initiation of Antiretroviral Therapy

Gkentzi, Despoina MD, MRCPCH*; Tebruegge, Marc MD, PhD, MRCPCH†‡§¶; Tudor-Williams, Gareth MD, MRCPCH†‖; Walters, Sam MD, FRCP†‖; Lyall, Hermione MD, FRCPCH†‖; Sharland, Mike MD, FRCPCH**; Doerholt, Katja MD, MSc, MRCPCH**

Pediatric Infectious Disease Journal: September 2014 - Volume 33 - Issue 9 - p 953–958
doi: 10.1097/INF.0000000000000331
HIV Reports

Background: Immune reconstitution syndrome (IRS) is a relatively common complication in HIV-infected adults starting combination antiretroviral therapy (cART). Data on IRS in HIV-infected children remain limited and are largely restricted to resource-limited settings. This study investigated the incidence, spectrum and outcome of IRS in a pediatric cohort in the United Kingdom.

Methods: Retrospective analysis of clinical events during the first 12 months after initiation of cART in 135 treatment-naïve, HIV-infected children in the United Kingdom over a 5-year period. Demographic and laboratory data were provided by the Collaborative HIV Paediatric Study.

Results: The median age at cART initiation was 6.6 years (interquartile range: 2.3–10.2). The median CD4 lymphocyte percentage (CD4%) at baseline was 15% (median CD4 lymphocyte count: 390 cells/μL). Eight patients (5.9%) developed IRS (incidence: 5.7/100 person years). The IRS events comprised: Bacillus Calmette-Guerin-related complications (local ulceration/lymphadenitis; n = 4), pulmonary tuberculosis (n = 1), Mycobacterium avium intracellulare infection (n = 1), combined tuberculosis/Mycobacterium avium intracellulare infection (n = 1) and cutaneous herpes simplex (n = 1). The mortality was significantly higher in children with IRS than in those without (P < 0.0001). The only statistically significant risk factor for IRS identified was increment in CD4 count at 12 months after starting cART (P = 0.03).

Conclusions: The incidence of IRS was significantly lower than previously reported from resource-limited settings, likely reflecting less profound immunodeficiency at cART initiation and fewer coexisting opportunistic infections in our cohort. However, IRS events were associated with considerable morbidity and mortality. Therefore, preventive strategies that can reduce the risk of IRS in children need to be identified.

From the *Paediatric Infectious Diseases Unit, St. George’s Hospital; Paediatric Infectious Diseases Unit, Imperial College Healthcare NHS Trust, London, United Kingdom; Department of Paediatrics, The University of Melbourne, Parkville, Australia; §Academic Unit of Clinical and Experimental Sciences, Faculty of Medicine; Institute for Life Sciences, University of Southampton, Southampton; Faculty of Medicine, Imperial College; and **Department of Paediatrics, St. George’s Medical School, London, United Kingdom.

Accepted for publication February 17, 2014.

D.G. and M.T. are joint first authors of this study.

The Collaborative HIV Paediatric Study is funded by the NHS (London Specialised Commissioning Group) and has received additional support from Bristol-Myers Squibb, Boehringer Ingelheim, GlaxoSmithKline, Roche, Abbott and Gilead Sciences.

The authors have no other funding or conflicts of interest to disclose.

Address for correspondence: Dr Despoina Gkentzi, Paediatric Infectious Diseases Unit, St. George’s Hospital, Cranmer Terrace, London, SW17 0RE, United Kingdom. E-mail:

© 2014 by Lippincott Williams & Wilkins, Inc.