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

Aabye MG, Ravn P, PrayGod G, Jeremiah K, Mugomela A, Jepsen M, Faurholt D, Range N, Friis H, Changalucha J, Andersen AB - PLoS ONE (2009)

Bottom Line: The QFT-IT was positive in 74% (119/161; 95% CI: 67-81%).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).However, since the test missed more than 10% of patients, its potential as a rule-out test for active TB disease is limited.

View Article: PubMed Central - PubMed

Affiliation: Department of Infectious Diseases, University of Copenhagen, Rigshospitalet, Copenhagen, Denmark. martine@aabye.com

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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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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pone-0004220-g003: 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.

Mentions: A positive trend of sensitivity with increasing CD4 cell count was observed for HIV-positive patients when stratifying CD4 cell counts into groups of <100, 100–200, 200–300, 300–400, 400–500, >500 (p = 0.03). We found a similar inverse trend with increasing proportion of indeterminate results with decreasing CD4 cell count (p = 0.03). When excluding indeterminate results no trend was observed for sensitivity and CD4 cell count (p = 0.44) (Figure 3). These findings were observed both when dividing CD4 cell counts into groups of pentiles and when dividing them into groups of hundreds. In HIV-positive patients, QFT-IT sensitivity was significantly lower in patients with CD4 cell count below compared to above 300 cells/µl (52 vs. 85%, p = 0.01). This was not the case for HIV-negative patients (90 vs. 78%, p = 0.35).


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

Aabye MG, Ravn P, PrayGod G, Jeremiah K, Mugomela A, Jepsen M, Faurholt D, Range N, Friis H, Changalucha J, Andersen AB - PLoS ONE (2009)

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.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2626632&req=5

pone-0004220-g003: 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.
Mentions: A positive trend of sensitivity with increasing CD4 cell count was observed for HIV-positive patients when stratifying CD4 cell counts into groups of <100, 100–200, 200–300, 300–400, 400–500, >500 (p = 0.03). We found a similar inverse trend with increasing proportion of indeterminate results with decreasing CD4 cell count (p = 0.03). When excluding indeterminate results no trend was observed for sensitivity and CD4 cell count (p = 0.44) (Figure 3). These findings were observed both when dividing CD4 cell counts into groups of pentiles and when dividing them into groups of hundreds. In HIV-positive patients, QFT-IT sensitivity was significantly lower in patients with CD4 cell count below compared to above 300 cells/µl (52 vs. 85%, p = 0.01). This was not the case for HIV-negative patients (90 vs. 78%, p = 0.35).

Bottom Line: The QFT-IT was positive in 74% (119/161; 95% CI: 67-81%).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).However, since the test missed more than 10% of patients, its potential as a rule-out test for active TB disease is limited.

View Article: PubMed Central - PubMed

Affiliation: Department of Infectious Diseases, University of Copenhagen, Rigshospitalet, Copenhagen, Denmark. martine@aabye.com

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.

Show MeSH
Related in: MedlinePlus