The Effects of HIV on the Sensitivity of a Whole Blood IFN-γ Release Assay in Zambian Adults with Active Tuberculosis

Abstract

BackgroundInterferon gamma release assays (IGRA) are replacing the tuberculin skin test (TST) as a diagnostic tool for Mycobacterium tuberculosis infection. However research into the test's performance in the high HIV-TB burden setting is scarce. This study aimed to define the sensitivity of an IGRA, QuantiFERON-TB® Gold In-Tube (QGIT), in adult Zambian patients with active smear-positive tuberculosis. Secondary outcomes focussed on the effect of HIV on the test's performance.Principal FindingsPatients attending government health clinics were recruited within 1 month of starting treatment for TB. Subjects were tested with QGIT and TST. T lymphocyte counts were estimated (CD3+, CD4+, CD8+). QGIT was performed for 112 subjects. 83/112 were QGIT positive giving an overall sensitivity of 74% [95%CI: 66,82]. A marked decrease in sensitivity was observed in HIV positive patients with 37/59 (63%) being QGIT positive compared to 31/37 (84%) HIV negative patients [chi2 p = 0.033]. Low CD4+ count was associated with increases in both indeterminate and false-negative results. Low CD4+ count in combination with high/normal CD8+ count was associated with false-negative results. TST was recorded for 92 patients, 62/92 were positive, giving a sensitivity of 67% [95%CI: 58,77]. Although there was little difference in the overall sensitivities, agreement between TST and QGIT was poor.ConclusionsQGIT was technically feasible with results in HIV negative subjects comparable to those achieved elsewhere. However, where under-treated HIV is prevalent, an increased proportion of both indeterminate and false-negative QGIT results can be expected in patients with active TB. The implications of this for the diagnosis of LTBI by QGIT is unclear. The diagnostic and prognostic relevance of IGRAs in high burden settings needs to be better characterised.

Cerebrospinal T-Cell Responses Aid in the Diagnosis of Tuberculous Meningitis in a Human Immunodeficiency Virus– and Tuberculosis-Endemic Population

“…It is likely that using the definite-TBM group in the analysis may overestimate sensitivity while using the definite plus the probable group may underestimate sensitivity. The true performance probably lies somewhere in between (39).…”

IP-10 release assays in the diagnosis of tuberculosis infection: current status and future directions

“…However, many studies have shown that the IGRAs, in particular the QFT-IT, render many indeterminate and possibly also false-negative results in HIV-infected individuals with a low CD4 cell count [13,14,[65][66][67][68][69][70][71][72]. Therefore, alternative approaches in this group of patients are necessary, but only few studies have evaluated IP-10 for this purpose.…”

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.…”

“…60,64 Despite impaired sensitivity, IFN-γ-based tests are clearly superior to TST for the diagnosis of active TB in these patients. 61, [65][66][67] IFN-γ-based tests may be of value in diagnosing TB in childhood, due to the absence of microbiological confirmation in a high proportion of cases. In a large prospective study, the sensitivity of T-SPOT.TB was 83%, and was not affected by HIV status.…”