Abstract

BackgroundInterferon gamma release assays (IGRAs) are used to diagnose latent tuberculosis infection. Two IGRAs are commercially available: the Quantiferon TB Gold In Tube (QFT-IT) and the T-SPOT.TB. There is debate as to which test to use in HIV+ individuals. Previous publications from high TB burden countries have raised concerns that the sensitivity of the QFT-IT assay, but not the T-SPOT.TB, may be impaired in HIV+ individuals with low CD4+ T-cell counts. We sought to compare the tests in a low TB burden setting.Methodology/Principal FindingsT-SPOT.TB, QFT-IT, and tuberculin skin tests (TST) were performed in HIV infected individuals. Results were related to patient characteristics. McNemar’s test, multivariate regression and correlation analysis were carried out using SPSS (SPSS Inc). 256 HIV infected patients were enrolled in the study. The median CD4+ T-cell count was 338 cells/µL (range 1–1328). 37 (14%) patients had a CD4+ T-cell count of <100 cells/µL. 46/256 (18% ) of QFT-IT results and 28/256 (11%) of T-SPOT.TB results were positive. 6 (2%) of QFT-IT and 18 (7%) of T-SPOT.TB results were indeterminate. An additional 9 (4%) of T-SPOT.TB results were unavailable as tests were not performed due to insufficient cells or clotting of the sample. We found a statistically significant association between lower CD4+ T-cell count and negative QFT-IT results (OR 1.055, p = 0.03), and indeterminate/unavailable T-SPOT.TB results (OR 1.079, p = 0.02).Conclusions/SignificanceIn low TB prevalence settings, the QFT-IT yields more positive and fewer indeterminate results than T-SPOT.TB. Negative results on the QFT-IT and indeterminate/unavailable results on the T-SPOT.TB were more common in individuals with low CD4+ T-cell counts.

Highlights

  • Tuberculosis is the most common opportunistic infection in HIV-infected individuals and is responsible for one-third of HIVassociated deaths [1]

  • Baseline characteristics of the patients are presented in table 1. 85/256 (33%) individuals were from countries of high TB prevalence. 171 (67%) were from countries of lowmoderate TB prevalence; of these, 112 (65%) reported one or more risk factors for TB exposure

  • In the remaining 9%, the median number of days between CD4+ T-cell count measurement and Interferon gamma release assays (IGRAs) testing was 64, range 6–150. 70% of HIV viral load measurements were concomitant with IGRA testing

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Summary

Introduction

Tuberculosis is the most common opportunistic infection in HIV-infected individuals and is responsible for one-third of HIVassociated deaths [1]. Interferon gamma release assays (IGRAs) are recently developed blood tests that measure in vitro responses to mycobacterial RD1 antigens which are unique to mycobacteria in the Mycobacterium tuberculosis complex (Mycobacterium tuberculosis, Mycobacterium bovis, Mycobacterium africanum) and Mycobacterium kansasii and are not present in M. bovis BCG [13]. There are two commercially available assays: the Quantiferon 3G In Tube (QFT-IT) assay (Cellestis, Carnegie, Australia), which utilises an ELISA technique to measure the amount of interferon gamma secreted in response to ESAT-6, CFP-10 and TB 7.7; and the T.SPOT-TB (Oxford Immunotec, Abingdon, UK), which uses an ELISPOT to quantify the number of cells producing interferon gamma in response to ESAT-6 and CFP-10. Interferon gamma release assays (IGRAs) are used to diagnose latent tuberculosis infection. Previous publications from high TB burden countries have raised concerns that the sensitivity of the QFT-IT assay, but not the T-SPOT.TB, may be impaired in HIV+ individuals with low CD4+ T-cell counts. We sought to compare the tests in a low TB burden setting

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