title: The role of targeted viral load testing in diagnosing virological failure in children on antiretroviral therapy with immunological failure.
abstract: OBJECTIVE
  To determine the improvement in positive predictive value of immunological failure criteria for identifying virological failure in HIV-infected children on antiretroviral therapy (ART) when a single targeted viral load measurement is performed in children identified as having immunological failure.
  
  
  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. Immunological failure was defined according to both WHO 2010 and United States Department of Health and Human Services (DHHS) 2008 criteria. Confirmed virological failure was defined as HIV-RNA >5000 copies/ml on two consecutive occasions <365 days apart in a child on ART for ≥18 months.
  
  
  RESULTS
  Among 2798 children on ART for ≥18 months [median (IQR) age 50 (21-84) months at ART initiation], the cumulative probability of confirmed virological failure by 42 months on ART was 6.3%. Using targeted viral load after meeting DHHS immunological failure criteria rather than DHHS immunological failure criteria alone increased positive predictive value from 28% to 82%. Targeted viral load improved the positive predictive value of WHO 2010 criteria for identifying confirmed virological failure from 49% to 82%.
  
  
  CONCLUSIONS
  The addition of a single viral load measurement in children identified as failing immunologically will prevent most switches to second-line treatment in virologically suppressed children.
authors.affiliation: School of Public Health and Family Medicine, University of Cape Town, Cape Town, South Africa  Empilweni Service and Research Unit, Rahima Moosa Mother and Child Hospital and University of Witwatersrand, Johannesburg, South Africa  Red Cross Children's Hospital and School of Child and Adolescent Health, University of Cape Town, Cape Town, South Africa  Wits Reproductive Health and HIV Institute (Harriet Shezi Children's Clinic, Chris Hani Baragwanath Hospital, Soweto), Faculty of Health Sciences, University of Witwatersrand, Johannesburg, South Africa  Tygerberg Academic Hospital, University of Stellenbosch, Stellenbosch, South Africa  Médecins Sans Frontières South Africa and Khayelitsha ART Programme, Khayelitsha, Cape Town, South Africa  Sinikithemba Clinic, McCord Hospital, Durban, South Africa  Gugulethu Community Health Centre and Desmond Tutu HIV Centre, Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, Cape Town, South Africa  Institute of Social and Preventive Medicine (ISPM), University of Bern, Bern, Switzerland.
authors.forename: Mary-Ann
authors.initials: MA
authors.lastname: Davies
authors.forename: Andrew
authors.initials: A
authors.lastname: Boulle
authors.forename: Karl
authors.initials: K
authors.lastname: Technau
authors.forename: Brian
authors.initials: B
authors.lastname: Eley
authors.forename: Harry
authors.initials: H
authors.lastname: Moultrie
authors.forename: Helena
authors.initials: H
authors.lastname: Rabie
authors.forename: Daniela
authors.initials: D
authors.lastname: Garone
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: D044966:Anti-Retroviral Agents / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D016903:Drug Monitoring / Q000379:methods; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D007223:Infant; D011237:Predictive Value of Tests; D012367:RNA, Viral / Q000097:blood; D013019:South Africa; D016896:Treatment Outcome; D019562:Viral Load
chemical_list: D044966:Anti-Retroviral Agents; D012367:RNA, Viral