Immunologic criteria are poor predictors of virologic outcome: implications for HIV treatment monitoring in resource-limited settings

Clin Infect Dis. 2011 Dec;53(12):1283-90. doi: 10.1093/cid/cir729.

Abstract

Background: Viral load (VL) quantification is considered essential for determining antiretroviral treatment (ART) success in resource-rich countries. However, it is not widely available in resource-limited settings where the burden of human immunodeficiency virus infection is greatest. In the absence of VL monitoring, switches to second-line ART are based on World Health Organization (WHO) clinical or immunologic failure criteria.

Methods: We assessed the performance of CD4 cell criteria to predict virologic outcomes in a large ART program in Nigeria. Laboratory monitoring consists of CD4 cell count and VL at baseline, then every 6 months. Failure was defined as 2 consecutive VLs >1000 copies/mL after at least 6 months of ART. Virologic outcomes were compared with the 3 WHO-defined immunologic failure criteria.

Results: A total of 9690 patients were included in the analysis (median follow-up, 33.2 months). A total of 1225 patients experienced failure by both immunologic and virologic criteria, 872 by virologic criteria only, and 1897 by immunologic criteria only. The sensitivity of CD4 cell criteria to detect viral failure was 58%, specificity was 75%, and the positive-predictive value was 39%. For patients with both virologic and immunologic failure, VL criteria identified failure significantly earlier than CD4 cell criteria (median, 10.4 vs 15.6 months; P < .0001).

Conclusions: Because of the low sensitivity of immunologic criteria, a substantial number of failures are missed, potentially resulting in accumulation of resistance mutations. In addition, specificity and predictive values are low, which may result in large numbers of unnecessary ART switches. Monitoring solely by immunologic criteria may result in increased costs because of excess switches to more expensive ART and development of drug-resistant virus.

Publication types

  • Comparative Study
  • Evaluation Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Anti-HIV Agents / administration & dosage*
  • CD4 Lymphocyte Count
  • Developing Countries
  • Drug Monitoring / methods*
  • Female
  • HIV Infections / diagnosis
  • HIV Infections / drug therapy*
  • HIV Infections / immunology*
  • HIV Infections / virology
  • Humans
  • Longitudinal Studies
  • Male
  • Nigeria
  • Predictive Value of Tests
  • Sensitivity and Specificity
  • Treatment Outcome
  • Viral Load

Substances

  • Anti-HIV Agents