title: The impact of HIV and antiretroviral therapy on TB risk in children: a systematic review and meta-analysis.
abstract: Children (<15 years) are vulnerable to TB disease following infection, but no systematic review or meta-analysis has quantified the effects of HIV-related immunosuppression or antiretroviral therapy (ART) on their TB incidence.
  
  
  
  Determine the impact of HIV infection and ART on risk of incident TB disease in children.
  
  
  
  We searched MEDLINE and Embase for studies measuring HIV prevalence in paediatric TB cases ('TB cohorts') and paediatric HIV cohorts reporting TB incidence ('HIV cohorts'). Study quality was assessed using the Newcastle-Ottawa tool. TB cohorts with controls were meta-analysed to determine the incidence rate ratio (IRR) for TB given HIV. HIV cohort data were meta-analysed to estimate the trend in log-IRR versus CD4%, relative incidence by immunological stage and ART-associated protection from TB.
  
  
  
  42 TB cohorts and 22 HIV cohorts were included. In the eight TB cohorts with controls, the IRR for TB was 7.9 (95% CI 4.5 to 13.7). HIV-infected children exhibited a reduction in IRR of 0.94 (95% credible interval: 0.83-1.07) per percentage point increase in CD4%. TB incidence was 5.0 (95% CI 4.0 to 6.0) times higher in children with severe compared with non-significant immunosuppression. TB incidence was lower in HIV-infected children on ART (HR: 0.30; 95% CI 0.21 to 0.39). Following initiation of ART, TB incidence declined rapidly over 12 months towards a HR of 0.10 (95% CI 0.04 to 0.25).
  
  
  
  HIV is a potent risk factor for paediatric TB, and ART is strongly protective. In HIV-infected children, early diagnosis and ART initiation reduces TB risk.
  
  
  
  CRD42014014276.
authors.affiliation: School of Health and Related Research, University of Sheffield, Sheffield, UK.
authors.forename: P J
authors.identifier: 0000-0001-5825-9347
authors.initials: PJ
authors.lastname: Dodd
authors.affiliation: Blizard Institute, Queen Mary University of London, London, UK.|Zvitambo Institute for Maternal and Child Health Research, Harare, Zimbabwe.
authors.forename: A J
authors.initials: AJ
authors.lastname: Prendergast
authors.affiliation: School of Health and Related Research, University of Sheffield, Sheffield, UK.
authors.forename: C
authors.initials: C
authors.lastname: Beecroft
authors.affiliation: Centre of International Child Health, Department of Paediatrics, Imperial College London, London, UK.|Vaccines & Immunity Theme, MRC Unit The Gambia, The Gambia.
authors.forename: B
authors.initials: B
authors.lastname: Kampmann
authors.affiliation: Centre of International Child Health, Department of Paediatrics, Imperial College London, London, UK.
authors.forename: J A
authors.identifier: 0000-0002-2296-2302
authors.initials: JA
authors.lastname: Seddon
mesh_terms: D019380:Anti-HIV Agents / Q000627:therapeutic use*; D002648:Child; D060085:Coinfection / Q000453:epidemiology* / Q000276:immunology; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy / Q000453:epidemiology* / Q000276:immunology; D006801:Humans; D016867:Immunocompromised Host; D015994:Incidence; D009894:Opportunistic Infections / Q000150:complications / Q000453:epidemiology* / Q000276:immunology; D018570:Risk Assessment / Q000379:methods; D014376:Tuberculosis / Q000150:complications / Q000453:epidemiology* / Q000276:immunology
chemical_list: D019380:Anti-HIV Agents
keywords: Tuberculosis