title: Risk of triple-class virological failure in children with HIV: a retrospective cohort study.
abstract: BACKGROUND
  In adults with HIV treated with antiretroviral drug regimens from within the three original drug classes (nucleoside or nucleotide reverse transcriptase inhibitors [NRTIs], non-NRTIs [NNRTIs], and protease inhibitors), virological failure occurs slowly, suggesting that long-term virological suppression can be achieved in most people, even in areas where access is restricted to drugs from these classes. It is unclear whether this is the case for children, the group who will need to maintain viral suppression for longest. We aimed to determine the rate and predictors of triple-class virological failure to the three original drugs classes in children.
  
  
  METHODS
  In the Collaboration of Observational HIV Epidemiological Research Europe, the rate of triple-class virological failure was studied in children infected perinatally with HIV who were aged less than 16 years, starting antiretroviral therapy (ART) with three or more drugs, between 1998 and 2008. We used Kaplan-Meier and Cox regression methods to investigate the risk and predictors of triple-class virological failure after ART initiation.
  
  
  RESULTS
  Of 1007 children followed up for a median of 4·2 (IQR 2·4-6·5) years, 237 (24%) were triple-class exposed and 105 (10%) had triple-class virological failure, of whom 29 never had a viral-load measurement less than 500 copies per mL. Incidence of triple-class virological failure after ART initiation increased with time, and risk by 5 years after ART initiation was 12·0% (95% CI 9·4-14·6). In multivariate analysis, older age at ART initiation was associated with increased risk of failure (p=0·02). Of 686 children starting ART with NRTIs and either a NNRTI or ritonavir-boosted protease inhibitor, the rate of failure was higher than in adults with heterosexually transmitted HIV (hazard ratio 2·2 [95% CI 1·6-3·0, p<0·0001]).
  
  
  CONCLUSIONS
  Findings highlight the challenges of attaining long-term viral suppression in children who will be taking life-long ART. Early identification of children not responding to ART, adherence support, particularly for children and adolescents aged 13 years or older starting ART, and ART simplification strategies are all needed to attain and sustain virological suppression.
  
  
  BACKGROUND
  UK Medical Research Council award G0700832.
authors.forename: Hannah
authors.initials: H
authors.lastname: Castro
authors.forename: Ali
authors.initials: A
authors.lastname: Judd
authors.forename: Diana M
authors.initials: DM
authors.lastname: Gibb
authors.forename: Karina
authors.initials: K
authors.lastname: Butler
authors.forename: Rebecca K
authors.initials: RK
authors.lastname: Lodwick
authors.forename: Ard
authors.initials: A
authors.lastname: van Sighem
authors.forename: Jose T
authors.initials: JT
authors.lastname: Ramos
authors.forename: Josiane
authors.initials: J
authors.lastname: Warsawski
authors.forename: Claire
authors.initials: C
authors.lastname: Thorne
authors.forename: Antoni
authors.initials: A
authors.lastname: Noguera-Julian
authors.forename: Niels
authors.initials: N
authors.lastname: Obel
authors.forename: Dominique
authors.initials: D
authors.lastname: Costagliola
authors.forename: Pat A
authors.initials: PA
authors.lastname: Tookey
authors.forename: Céline
authors.initials: C
authors.lastname: Colin
authors.forename: Jesper
authors.initials: J
authors.lastname: Kjaer
authors.forename: Jesper
authors.initials: J
authors.lastname: Grarup
authors.forename: Genevieve
authors.initials: G
authors.lastname: Chene
authors.forename: Andrew
authors.initials: A
authors.lastname: Phillips
mesh_terms: D000293:Adolescent; D044966:Anti-Retroviral Agents / Q000145:classification / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000635:transmission / Q000821:virology; D006801:Humans; D007223:Infant; D018445:Infectious Disease Transmission, Vertical; D053208:Kaplan-Meier Estimate; D008297:Male; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D012306:Risk; D017211:Treatment Failure; D019562:Viral Load
chemical_list: D044966:Anti-Retroviral Agents