The effects of HIV on the sensitivity of a whole blood IFN-gamma release assay in Zambian adults with active tuberculosis

PLoS One. 2008 Jun 18;3(6):e2489. doi: 10.1371/journal.pone.0002489.


Background: Interferon 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 findings: Patients 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 [chi(2) 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.

Conclusions: QGIT 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Female
  • HIV / physiology*
  • Humans
  • Interferon-gamma / blood*
  • Male
  • Prognosis
  • Sensitivity and Specificity
  • T-Lymphocyte Subsets
  • Tuberculosis / blood*
  • Zambia


  • Interferon-gamma