title: Incidence, spectrum and outcome of immune reconstitution syndrome in HIV-infected children after initiation of antiretroviral therapy.
abstract: 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.
authors.affiliation: 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.
authors.forename: Despoina
authors.initials: D
authors.lastname: Gkentzi
authors.forename: Marc
authors.initials: M
authors.lastname: Tebruegge
authors.forename: Gareth
authors.initials: G
authors.lastname: Tudor-Williams
authors.forename: Sam
authors.initials: S
authors.lastname: Walters
authors.forename: Hermione
authors.initials: H
authors.lastname: Lyall
authors.forename: Mike
authors.initials: M
authors.lastname: Sharland
authors.forename: Katja
authors.initials: K
authors.lastname: Doerholt
mesh_terms: D044966:Anti-Retroviral Agents / Q000009:adverse effects*; D001500:BCG Vaccine / Q000009:adverse effects; D018791:CD4 Lymphocyte Count; D002648:Child; D002675:Child, Preschool; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology*; D006561:Herpes Simplex / Q000209:etiology; D006801:Humans; D054019:Immune Reconstitution Inflammatory Syndrome / Q000453:epidemiology* / Q000276:immunology*; D015994:Incidence; D007223:Infant; D008199:Lymphadenitis / Q000209:etiology; D008297:Male; D015270:Mycobacterium avium-intracellulare Infection / Q000209:etiology; D012189:Retrospective Studies; D017193:Skin Diseases, Viral / Q000209:etiology; D014397:Tuberculosis, Pulmonary / Q000209:etiology
chemical_list: D044966:Anti-Retroviral Agents; D001500:BCG Vaccine