Abstract

BackgroundDiagnosis and treatment of latent tuberculosis infection (LTBI) is the most effective strategy to control tuberculosis (TB) among patients with HIV infection. The tuberculin skin test (TST) was the only available method to identify LTBI. The aim of the present work was to evaluate the usefulness of the interferon-gamma release assays (IGRAs): QuantiFERON-tuberculosis (TB) Gold-In-Tube test (QFG) and T-SPOT.TB for the diagnosis of LTBI in a diverse cohort of HIV-infected patients.MethodsA prospective study was carried out in consecutive patients cared for in a single institution in Spain from January 2009 to October 2010. IGRAs and TST were performed simultaneously. TST induration ≥ 5 mm was considered positive.ResultsQFG, T-SPOT.TB and TST were performed in 373 subjects. Median CD4 cell count was 470/μl with a median nadir of 150/μl. TST, QFG and T-SPOT.TB were positive in 13.3%, 7.5% and 18.5% cases respectively. Among 277 patients with neither past or current TB nor previous treatment for LTBI and who had TST results, a positive TST result was obtained in 20 (7.2%) cases. When adding QFG results to TST, there were a total of 26 (8.6%) diagnoses of LTBI. When the results of both IGRAs were added, the number of diagnoses increased to 54 (17.9%) (incremental difference: 10.7% [95% confidence interval [CI]:5.3-16.2%] [p < 0.001]), and when both IGRAs were added, the number of diagnoses reached 56 (18.5%) (incremental difference: 11.3% [95% CI:5.7%–16.9%] [p < 0.001]). Patients with a CD4 cell count greater than 500 cells/μl and prior stay in prison were more likely to have a diagnosis of LTBI by TST and/or QFG and/or T-SPOT.TB (adjusted odds ratio [aOR]: 3.8; 95% CI, 1.4 – 9.9; and aOR: 3.3; 95% CI, 1.3 – 8.3, respectively).ConclusionsIGRAs were more sensitive than TST for diagnosis of M. tuberculosis infection in HIV-infected patients. Dual sequential testing with TST and IGRAs may be the optimal approach for LTBI screening in this population.

Highlights

  • Diagnosis and treatment of latent tuberculosis infection (LTBI) is the most effective strategy to control tuberculosis (TB) among patients with HIV infection

  • The interferon-gamma release assays (IGRAs) measure T-cell release of interferon-γ (IFN-γ) following stimulation by antigens that are unique to M. tuberculosis including early-secreted antigenic target 6 (ESAT-6) and culture filtrate protein 10 (CFP-10), which are encoded by genes located within the region of difference 1 (RD1) segment of the M. tuberculosis genome [5]

  • QuantiFERON-TB Gold In-Tube test (QFG) (Cellestis, Carnegie, Australia) measures the level of soluble IFN-γ produced in whole blood by enzyme-linked immunosorbent assay (ELISA), and the T-SPOT.TB (Oxford Immunotec, Abingdon, UK) assay detects the number of IFN-γ -producing cells represented as spot-forming units (SFU)

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Summary

Introduction

Diagnosis and treatment of latent tuberculosis infection (LTBI) is the most effective strategy to control tuberculosis (TB) among patients with HIV infection. The interferon-gamma release assays (IGRAs) measure T-cell release of interferon-γ (IFN-γ) following stimulation by antigens that are unique to M. tuberculosis including early-secreted antigenic target 6 (ESAT-6) and culture filtrate protein 10 (CFP-10), which are encoded by genes located within the region of difference 1 (RD1) segment of the M. tuberculosis genome [5]. These antigens are more specific for M. tuberculosis than those in the purified protein derivate (PPD) used in the TST because they are not shared with any BacilleCalmette-Guérin (BCG) vaccine strains. The IGRAs present practical and theoretical advantages over TST, and the US Centers for Disease Control (CDC) have released guidelines for using these assays to detect M. tuberculosis infection in certain circumstances [6]

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