Accuracy of WHO CD4 cell count criteria for virological failure of antiretroviral therapy

Trop Med Int Health. 2009 Oct;14(10):1220-5. doi: 10.1111/j.1365-3156.2009.02338.x. Epub 2009 Jul 14.


Objectives: 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anti-Retroviral Agents / therapeutic use*
  • CD4 Lymphocyte Count / methods
  • CD4 Lymphocyte Count / standards*
  • Female
  • HIV Infections / drug therapy
  • HIV Infections / immunology*
  • HIV Infections / virology
  • HIV-1 / immunology*
  • Humans
  • Immunity, Cellular
  • Male
  • RNA, Viral / analysis
  • RNA, Viral / immunology
  • Risk Factors
  • Treatment Failure
  • Viral Load / standards*
  • World Health Organization


  • Anti-Retroviral Agents
  • RNA, Viral