title: Analysis of the optimal cut-point for HIV-p24 antigen testing to diagnose HIV infection in HIV-exposed children from resource-constrained settings.
abstract: BACKGROUND
  Nucleic-acid-testing (NAT) to diagnose HIV infection in children under age 18 months provides a barrier to HIV-testing in exposed children from resource-constrained settings. The ultrasensitive HIV-p24-antigen (Up24) assay is cheaper and easier to perform and is sensitive (84-98%) and specific (98-100%). The cut-point optical density (OD) selected for discriminating between positive and negative samples may need assessment due to regional differences in mother-to-child HIV-transmission rates.
  
  
  OBJECTIVE
  We used receiver operator characteristics (ROC) curves and logistic regression analyses to assess the effect of various cut-points on the diagnostic performance of Up24 for HIV-infection status among HIV-exposed children. Positive and negative predictive values at different rates of disease prevalence were also estimated.
  
  
  METHODS
  A study of Up24 testing on dried blood spot (DBS) samples collected from 278 HIV-exposed Haitian children, 3-24-months of age, in whom HIV-infection status was determined by NAT on the same DBS card.
  
  
  RESULTS
  The sensitivity and specificity of Up24 varied by the cut-point-OD value selected. At a cut-point-OD of 8-fold the standard deviation of the negative control (NCSD), sensitivity and specificity of Up24 were maximized [87.8% (95% CI, 83.9-91.6) and 92% (95% CI, 88.8-95.2), respectively]. In lower prevalence settings (5%), positive and negative predictive values of Up24 were maximal (75.9% and 98.8%, respectively) at a cut-point-OD that was 15-fold the NCSD.
  
  
  CONCLUSIONS
  In low prevalence settings, a high degree of specificity can be achieved with Up24 testing of HIV-exposed children when a higher cut-point OD is used; a feature that may facilitate more frequent use of Up24 antigen testing for HIV-exposed children.
authors.affiliation: Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
authors.forename: M
authors.initials: M
authors.lastname: Tamhane
authors.forename: B
authors.initials: B
authors.lastname: Gautney
authors.forename: C
authors.initials: C
authors.lastname: Shiu
authors.forename: N
authors.initials: N
authors.lastname: Segaren
authors.forename: L
authors.initials: L
authors.lastname: Jeannis
authors.forename: C
authors.initials: C
authors.lastname: Eustache
authors.forename: Y
authors.initials: Y
authors.lastname: Simeon-Fadois
authors.forename: Y H
authors.initials: YH
authors.lastname: Chen
authors.forename: D
authors.initials: D
authors.lastname: De
authors.forename: S
authors.initials: S
authors.lastname: Irivinti
authors.forename: P
authors.initials: P
authors.lastname: Tamma
authors.forename: C B
authors.initials: CB
authors.lastname: Thompson
authors.forename: S
authors.initials: S
authors.lastname: Khamadi
authors.forename: G K
authors.initials: GK
authors.lastname: Siberry
authors.forename: D
authors.initials: D
authors.lastname: Persaud
mesh_terms: D015492:AIDS Serodiagnosis / Q000379:methods; D002675:Child, Preschool; D015331:Cohort Studies; D006678:HIV / Q000276:immunology*; D016655:HIV Core Protein p24 / Q000032:analysis* / Q000097:blood / Q000276:immunology; D015658:HIV Infections / Q000097:blood / Q000175:diagnosis* / Q000276:immunology; D006679:HIV Seropositivity / Q000276:immunology; D006295:Health Resources; D006801:Humans; D007223:Infant; D016015:Logistic Models; D015995:Prevalence; D012372:ROC Curve
chemical_list: D016655:HIV Core Protein p24