title: Accuracy of immunological criteria for identifying virological failure in children on antiretroviral therapy - the IeDEA Southern Africa Collaboration.
abstract: OBJECTIVE
  To determine the diagnostic accuracy of World Health Organization (WHO) 2010 and 2006 as well as United States Department of Health and Human Services (DHHS) 2008 definitions of immunological failure for identifying virological failure (VF) in children on antiretroviral therapy (ART).
  
  
  METHODS
  Analysis of data from children (<16 years at ART initiation) at South African ART sites at which CD4 count/per cent and HIV-RNA monitoring are performed 6-monthly. Incomplete virological suppression (IVS) was defined as failure to achieve ≥1 HIV-RNA ≤400 copies/ml between 6 and 15 months on ART and viral rebound (VR) as confirmed HIV-RNA ≥5000 copies/ml in a child on ART for ≥18 months who had achieved suppression during the first year on treatment.
  
  
  RESULTS
  Among 3115 children [median (interquartile range) age 48 (20-84) months at ART initiation] on treatment for ≥1 year, sensitivity of immunological criteria for IVS was 10%, 6% and 26% for WHO 2006, WHO 2010 and DHHS 2008 criteria, respectively. The corresponding positive predictive values (PPV) were 31%, 20% and 20%. Diagnostic accuracy for VR was determined in 2513 children with ≥18 months of follow-up and virological suppression during the first year on ART with sensitivity of 5% (WHO 2006/2010) and 27% (DHHS 2008). PPV results were 42% (WHO 2010), 43% (WHO 2006) and 20% (DHHS 2008).
  
  
  CONCLUSIONS
  Current immunological criteria are unable to correctly identify children failing ART virologically. Improved access to viral load testing is needed to reliably identify VF in children.
authors.affiliation: School of Public Health and Family Medicine, University of Cape Town, Cape Town, South Africa. mary-ann.davies@uct.ac.za
authors.forename: Mary-Ann
authors.initials: MA
authors.lastname: Davies
authors.forename: Andrew
authors.initials: A
authors.lastname: Boulle
authors.forename: Brian
authors.initials: B
authors.lastname: Eley
authors.forename: Harry
authors.initials: H
authors.lastname: Moultrie
authors.forename: Karl
authors.initials: K
authors.lastname: Technau
authors.forename: Helena
authors.initials: H
authors.lastname: Rabie
authors.forename: Gilles
authors.initials: G
authors.lastname: van Cutsem
authors.forename: Janet
authors.initials: J
authors.lastname: Giddy
authors.forename: Robin
authors.initials: R
authors.lastname: Wood
authors.forename: Matthias
authors.initials: M
authors.lastname: Egger
authors.forename: Olivia
authors.initials: O
authors.lastname: Keiser
mesh_terms: D000293:Adolescent; D000353:Africa, Southern; D044966:Anti-Retroviral Agents / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D002648:Child; D002675:Child, Preschool; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D006801:Humans; D007223:Infant; D008137:Longitudinal Studies; D011237:Predictive Value of Tests; D017211:Treatment Failure; D019562:Viral Load; D014944:World Health Organization
chemical_list: D044966:Anti-Retroviral Agents