The Impact of HIV Infection and CD4 Cell Count on the Performance of an Interferon Gamma Release Assay in Patients with Pulmonary Tuberculosis

Abstract

BackgroundThe 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 Findings161 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/µl) 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/SignificanceSensitivity 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.

Sensitivity of C-Tb: a novel RD-1-specific skin test for the diagnosis of tuberculosis infection

“…This is a well-known effect of HIV-induced immunosuppression [25][26][27][28]. A drop in the magnitude of responses was evident in patients with CD4 counts <400 cells·mm -3 .…”

HIV and Tuberculosis: a Deadly Human Syndemic

“…For the T-SPOT.TB assay, the sensitivity was between 79 and 95% and the specificity was between 64% and 100% for active TB in HIV-infected patients (74). The sensitivity of the QFT-GIT test for culture-confirmed pulmonary TB in HIV-infected patients ranged from 65% to 91% in previously reported studies, and the likelihood of indeterminate results increased with lower CD4 counts (1,9,74,158,177,242,254). Aabye et al found that 22% of HIV-infected patients with culture-confirmed pulmonary TB had indeterminate results with the QFT-GIT test, and patients with CD4 counts below 300 cells/l were nearly 3 times as likely to have indeterminate results as patients with CD4 counts above 300 cells/l (1).…”

Diagnosis of tuberculosis infection using interferon-γ-based assays

“…58 In 4 studies that compared performance of QFT-IT in HIV-infected and non-infected adults with active TB, mean sensitivity was 64% in HIV-infected patients and 79% in non-HIV-infected patients. [59][60][61][62] Although the overall sensitivity of T-SPOT.TB is higher than that of QFT-IT in otherwise healthy people, data from head-to-head comparisons in HIV-infected patients are scarce. 60,63,64 In three studies, covering a total of 39 patients with culture-confirmed TB, QFT-IT and T-SPOT.TB detected 74% and 82% of cases respectively.…”