title: Accuracy of WHO CD4 cell count criteria for virological failure of antiretroviral therapy.
abstract: OBJECTIVE
  To examine the accuracy of the World Health Organization immunological criteria for virological failure of antiretroviral treatment.
  
  
  METHODS
  Analysis of 10 treatment programmes in Africa and South America that monitor both CD4 cell counts and HIV-1 viral load. Adult patients with at least two CD4 counts and viral load measurements between month 6 and 18 after starting a non-nucleoside reverse transcriptase inhibitor-based regimen were included. WHO immunological criteria include CD4 counts persistently <100 cells/microl, a fall below the baseline CD4 count, or a fall of >50% from the peak value. Virological failure was defined as two measurements > or =10 0000 copies/ml (higher threshold) or > or =500 copies/ml (lower threshold). Measures of accuracy with exact binomial 95% confidence intervals (CI) were calculated.
  
  
  RESULTS
  A total of 2009 patients were included. During 1856 person-years of follow up 63 patients met the immunological criteria and 35 patients (higher threshold) and 95 patients (lower threshold) met the virological criteria. Sensitivity [95% confidence interval (CI)] was 17.1% (6.6-33.6%) for the higher and 12.6% (6.7-21.0%) for the lower threshold. Corresponding results for specificity were 97.1% (96.3-97.8%) and 97.3% (96.5-98.0%), for positive predictive value 9.5% (3.6-19.6%) and 19.0% (10.2-30.9%) and for negative predictive value 98.5% (97.9-99.0%) and 95.7% (94.7-96.6%).
  
  
  CONCLUSIONS
  The positive predictive value of the WHO immunological criteria for virological failure of antiretroviral treatment in resource-limited settings is poor, but the negative predictive value is high. Immunological criteria are more appropriate for ruling out than for ruling in virological failure in resource-limited settings.
authors.affiliation: Institute of Social and Preventive Medicine (ISPM), University of Bern, CH-3012 Bern, Switzerland. okeiser@ispm.unibe.ch
authors.forename: Olivia
authors.initials: O
authors.lastname: Keiser
authors.forename: Patrick
authors.initials: P
authors.lastname: MacPhail
authors.forename: Andrew
authors.initials: A
authors.lastname: Boulle
authors.forename: Robin
authors.initials: R
authors.lastname: Wood
authors.forename: Mauro
authors.initials: M
authors.lastname: Schechter
authors.forename: François
authors.initials: F
authors.lastname: Dabis
authors.forename: Eduardo
authors.initials: E
authors.lastname: Sprinz
authors.forename: Matthias
authors.initials: M
authors.lastname: Egger
mesh_terms: D000328:Adult; D044966:Anti-Retroviral Agents / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count / Q000379:methods / Q000592:standards*; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular; D008297:Male; D012367:RNA, Viral / Q000032:analysis / Q000276:immunology; D012307:Risk Factors; D017211:Treatment Failure; D019562:Viral Load / Q000592:standards*; D014944:World Health Organization
chemical_list: D044966:Anti-Retroviral Agents; D012367:RNA, Viral