The impact of HIV infection and CD4 cell count on the performance of an interferon gamma release assay in patients with pulmonary tuberculosis

PLoS One. 2009;4(1):e4220. doi: 10.1371/journal.pone.0004220. Epub 2009 Jan 19.

Abstract

Background: The performance of the tuberculosis specific Interferon Gamma Release Assays (IGRAs) has not been sufficiently documented in tuberculosis- and HIV-endemic settings. This study evaluated the sensitivity of the QuantiFERON TB-Gold In-Tube (QFT-IT) in patients with culture confirmed pulmonary tuberculosis (PTB) in a TB- and HIV-endemic population and the effect of HIV-infection and CD4 cell count on test performance.

Methodology/principal findings: 161 patients with sputum culture confirmed PTB were subjected to HIV- and QFT-IT testing and measurement of CD4 cell count. The QFT-IT was positive in 74% (119/161; 95% CI: 67-81%). Sensitivity was higher in HIV-negative (75/93) than in HIV-positive (44/68) patients (81% vs. 65%, p = 0.02) and increased with CD4 cell count in HIV-positive patients (test for trend p = 0.03). 23 patients (14%) had an indeterminate result and this proportion decreased with increasing CD4 cell count in HIV-positive patients (test for trend p = 0.03). Low CD4 cell count (<300 cells/microl) did not account for all QFT-IT indeterminate nor all negative results. Sensitivity when excluding indeterminate results was 86% (95% CI: 81-92%) and did not differ between HIV-negative and HIV-positive patients (88 vs. 83%, p = 0.39).

Conclusions/significance: Sensitivity of the QFT-IT for diagnosing active PTB infection was reasonable when excluding indeterminate results and in HIV-negative patients. However, since the test missed more than 10% of patients, its potential as a rule-out test for active TB disease is limited. Furthermore, test performance is impaired by low CD4 cell count in HIV-positive patients and possibly by other factors as well in both HIV-positive and HIV-negative patients. This might limit the potential of the test in populations where HIV-infection is prevalent.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Biochemistry / methods
  • CD4-Positive T-Lymphocytes / metabolism*
  • Female
  • HIV Infections / blood*
  • HIV Infections / complications*
  • HIV Seropositivity
  • Humans
  • Interferon-gamma / metabolism*
  • Male
  • Prevalence
  • Reagent Kits, Diagnostic
  • Sensitivity and Specificity
  • Sputum / metabolism
  • Tanzania
  • Tuberculosis, Pulmonary / blood*
  • Tuberculosis, Pulmonary / complications*

Substances

  • Reagent Kits, Diagnostic
  • Interferon-gamma