title: Prediction of treatment failure using 2010 World Health Organization Guidelines is associated with high misclassification rates and drug resistance among HIV-infected Cambodian children.
abstract: BACKGROUND
  Antiretroviral therapy (ART) in resource-limited settings (RLSs) is monitored clinically and immunologically, according to World Health Organization (WHO) or national guidelines. Revised WHO pediatric guidelines were published in 2010, but their ability to accurately identify virological failure is unclear.
  
  
  METHODS
  We evaluated performance of WHO 2010 guidelines and compared them with WHO 2006 and Cambodia 2011 guidelines among children on ≥6 months of first-line ART at Angkor Hospital for Children between January 2005 and September 2010. We determined sensitivity, specificity, positive and negative predictive values, and accuracy using bootstrap resampling to account for multiple tests per child. Human immunodeficiency virus (HIV) resistance was compared between those correctly and incorrectly identified by each guideline.
  
  
  RESULTS
  Among 457 children with 1079 viral loads (VLs), 20% had >400 copies/mL. For children with WHO stage 1/2 HIV, misclassification as failure (met CD4 failure criteria, but VL undetectable) was 64% for WHO 2006 guidelines, 33% for WHO 2010 guidelines, and 81% for Cambodia 2011 guidelines; misclassification as success (did not meet CD4 failure, but VL detectable) was 11%, 12%, and 12%, respectively. For children with WHO stage 3/4 HIV, misclassification as failure was 35% for WHO 2006 guidelines, 40% for WHO 2010 guidelines, and 43% for Cambodia 2011 guidelines; misclassification as success was 13%, 24%, and 21%, respectively. Compared with WHO 2006 guidelines, WHO 2010 guidelines significantly increased the risk of misclassification as success in stage 3/4 HIV (P < .05). The WHO 2010 guidelines failed to identify 98% of children with extensive reverse-transcriptase resistance.
  
  
  CONCLUSIONS
  In our cohort, lack of virological monitoring would result in unacceptable treatment failure misclassification, leading to premature ART switch and resistance accumulation. Affordable virological monitoring suitable for use in RLSs is desperately needed.
authors.affiliation: Division of Infectious Diseases, Alpert Medical School, Brown University, Providence, Rhode Island, USA. westley.ben@gmail.com
authors.forename: Benjamin P
authors.initials: BP
authors.lastname: Westley
authors.forename: Allison K
authors.initials: AK
authors.lastname: DeLong
authors.forename: Chhraing S
authors.initials: CS
authors.lastname: Tray
authors.forename: Dim
authors.initials: D
authors.lastname: Sophearin
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Dufort
authors.forename: Eric
authors.initials: E
authors.lastname: Nerrienet
authors.forename: Leeann
authors.initials: L
authors.lastname: Schreier
authors.forename: Joseph I
authors.initials: JI
authors.lastname: Harwell
authors.forename: Rami
authors.initials: R
authors.lastname: Kantor
mesh_terms: D000293:Adolescent; D019380:Anti-HIV Agents / Q000008:administration & dosage*; D015415:Biomarkers; D002160:Cambodia; D002648:Child; D002675:Child, Preschool; D015510:Clinical Medicine / Q000379:methods*; D016903:Drug Monitoring / Q000379:methods*; D024882:Drug Resistance, Viral; D005260:Female; D017408:Guidelines as Topic; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology*; D006801:Humans; D007223:Infant; D008297:Male; D011237:Predictive Value of Tests; D012680:Sensitivity and Specificity; D017211:Treatment Failure; D014944:World Health Organization
chemical_list: D019380:Anti-HIV Agents; D015415:Biomarkers