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

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

Martine G Aabye  1 , Pernille Ravn, George PrayGod, Kidola Jeremiah, Apolinary Mugomela, Maria Jepsen, Daniel Faurholt, Nyagosya Range, Henrik Friis, John Changalucha, Aase B Andersen
Affiliations

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

Martine G Aabye et al. PLoS One. 2009.

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.

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Conflict of interest statement

Competing Interests: Pernille Ravn was a consultant for Cellestis Ltd. in 2006 to develop their clinical guidelines and received a single payment of €2000.

Figures

Figure 1
Figure 1. Antigen dependent and mitogen induced absolute IFN-γ levels by QuantiFERON-TB® Gold In-tube test result in HIV-negative and HIV-positive patients respectively.
Horisontal lines represent medians. Dotted lines represent the applied cut-off values as recommended by the manufacturer: 0.35 IU/ml for antigen (ESAT-6, CFP-10, TB7.7) dependent IFN-γ production and 0.50 IU/ml for mitogen (PHA) induced IFN-γ production respectively. The assay is not able to quantify values above 10 IU/ml why values above this limit were assigned the value 10 IU/ml. No significant differences in median levels between HIV-positive and HIV-negative were observed.
Figure 2
Figure 2. Antigen dependent and mitogen induced absolute IFN-γ levels by HIV-status and CD4 cell count group.
Horisontal lines represent medians with interquartile range. Dotted lines represent the applied cut-off values as recommended by the manufacturer: 0.35 IU/ml for antigen (ESAT-6, CFP-10, TB7.7) dependent IFN-γ production and 0.50 IU/ml for mitogen (PHA) induced IFN-γ production respectively. The assay is not able to quantify values above 10 IU/ml why values above this limit were assigned the value 10 IU/ml.
Figure 3
Figure 3. Influence of CD4 cell count on performance of the QuantiFERON-TB® Gold In-tube test in HIV-positive patients.
For HIV-positive patients the % of indeterminate and positive test responders respectively was grouped by the individual number of CD4 cells/µl. P-values are for Cochrane-Armitage test for trend. A similar relationship was not found in HIV-negative patients. The number of patients in each CD4 cell group was: 0–99: 5, 100–199: 17, 200–299: 20, 300–399∶6, 400–499∶6, >500∶14. QFT-IT: QuantiFERON-TB® Gold In-tube test.
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