Detection and Prediction of Active Tuberculosis Disease by a Whole-Blood Interferon-gamma Release Assay in HIV-1-Infected Individuals
ABSTRACT The sensitivity of whole-blood interferon-gamma release assays to detect or predict active tuberculosis in individuals infected with human immunodeficiency virus type 1 (HIV-1) has as yet not been determined. Methods. In this prospective, longitudinal, single-center study, 830 HIV-1-infected patients underwent testing with the QuantiFERON-TB Gold In-Tube (QFT-GIT) assay. Clinical screening for active tuberculosis was performed at least every 3 months for a median follow-up time of 19 months.
At baseline, the QFT-GIT assay yielded positive or indeterminate results in 44 (5.3%) and 47 (5.7%) of the 830 patients, respectively. A positive QFT-GIT assay result occurred at significantly higher frequencies among black individuals than among white individuals (odds ratio, 4.84; 95% confidence interval, 2.25-9.97; P< .001), among patients from Africa than among patients from Austria (odds ratio, 6.57; 95% confidence interval, 2.99-14.25; P< .001), and among patients from high-prevalence countries than among patients from low-prevalence countries (odds ratio, 5.86; 95% confidence interval, 2.41-13.44; P< .001). In patients with indeterminate QFT-GIT assay results, both median actual and nadir CD4(+) T cell counts were significantly lower than in patients with interpretable QFT-GIT assay results (P< .001). At the time of baseline QFT-GIT screening, active tuberculosis was found in 7 (15.9%) of 44 individuals with a positive result and in 1 (0.1%) of 739 patients with a negative result. During the follow-up period, however, progression to active tuberculosis occurred exclusively in patients with a positive QFT-GIT assay result, at a rate of 8.1% (3 of 37 patients; P< .001). Collectively, the sensitivity of the QFT-GIT assay for active tuberculosis was 90.9% (95% confidence interval, 62.3%-98.4%).
Our results suggest that the QFT-GIT assay may be a sensitive tool for the detection and prediction of active tuberculosis in HIV-1-infected individuals.
SourceAvailable from: Anne Ma Dyrhol-Riise[Show abstract] [Hide abstract]
ABSTRACT: Background: Interferon-gamma release assays (IGRA) serve as immunodiagnostics of tuberculosis (TB) infection to identify individuals with latent TB infection (LTBI) eligible for preventive anti-TB therapy. In this longitudinal study of HIV-infected LTBI patients we have observed for possible progression to active TB as well as evaluated repeated IGRA testing in a TB low-endemic setting. Methods: QuantiFERON TB-Gold In-tube® assay (QFT), TB-SPOT.TB® (TSPOT) and tuberculin skin test (TST) were performed on 298 HIV-patients recruited from seven out-patient clinics in Norway. Patients with active TB, LTBI and negative IGRA were followed with repeat QFTs and clinical evaluation over a period of 24 months. Results: Seven HIV-patients (median CD4 count 270; IQR 50¿340) were diagnosed with active TB at inclusion, all IGRA positive. Sixty-four (21%) HIV-patients (median CD4 count 471; IQR 342+-638) were diagnosed with LTBI and of these 39 (61%) received TB preventive treatment. Neither treated nor untreated HIV-infected LTBI patients developed active TB during the 24 months. At baseline, the median interferon-gamma (INF-gamma) level measured by QFT was 3.48 IU/ml (IQR 0.94 +- 8.91 IU/ml) for treated LTBI compared to 1.13 IU/ml (IQR 0.47 +- 4.25 IU/ml) for untreated LTBI patients (p=0.029). The QFT reversion rates were 75% for active TB, 23% for treated LTBI and 44% for untreated LTBI, whereas the conversion rate for the non-TB group was 7% despite no new TB exposure. There was no significant difference in the trend of INF-gamma levels over time between treated and untreated LTBI patients. Conclusion: The prevalence of LTBI is high among HIV-patients, but the risk of developing active TB seems to be low in patients with high CD4 counts in this TB low-endemic setting. In several patients, especially with baseline IFN-gamma levels close to cut-offs, the QFT tests reverted to negative independent of preventive anti-TB treatment indicating possibly false positive tests. This highlights the importance of defining reliable cut-offs for immunodiagnostic tests and deferring preventive therapy in selected patients. Randomized studies with longer follow-up time are needed to identify HIV-patients that would benefit from LTBI treatment in a TB low-endemic setting.BMC Infectious Diseases 12/2014; 14(1):667. DOI:10.1186/s12879-014-0667-0 · 2.56 Impact Factor
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ABSTRACT: Rationale: In the absence of active tuberculosis, a positive tuberculin-skin-test (TST) or interferon-γ release assay (IGRA) result defines latent infection with Mycobacterium tuberculosis, although test-results may vary depending on immunodeficiency. Objectives: This study compared the performance of TST and IGRAs in five different groups of immunocompromised patients, and evaluated their ability to identify those at risk for development of tuberculosis. Methods: Immunocompromised patients with HIV-infection, chronic renal failure, rheumatoid arthritis, solid-organ or stem-cell transplantation, and healthy controls were evaluated head-to-head by the TST, QuantiFERON-TB-Gold in-tube test (ELISA) and T-SPOT.TB test (ELISPOT) at 17 centers in 11 European countries. Development of tuberculosis was assessed during follow-up. Main results: Frequencies of positive test-results varied from 8.7-15.9% in HIV-infection (n=768), 25.3-30.6% in chronic renal failure (n=270), 25.0-37.2% in rheumatoid arthritis (n=199), 9.0-20.0% in solid-organ transplant-recipients (n=197), 0-5.8% in stem-cell transplant-recipients (n=103), and 11.2-15.2% in immunocompetent controls (n=211). Eleven patients (10 with HIV-infection and one solid-organ transplant-recipient) developed tuberculosis during a median follow-up of 1.8 (IQR 0.2-3.0) years. Six of the 11 patients had a negative or indeterminate test-result in all three tests at the time of screening. Tuberculosis incidence was generally low, but higher in HIV-infected individuals with a positive TST (3.25 cases/100 person-years) than with a positive ELISA (1.31 cases/100 person-years) or ELISPOT-result (1.78 cases/100 person-years). No cases of tuberculosis occurred in patients who received preventive chemotherapy. Conclusions: Among immunocompromised patients evaluated in this study, progression towards tuberculosis was highest in HIV-infected individuals and was poorly predicted by TST or IGRAs Clinical trial registration information available at www.clinicaltrials.gov, ID NCT00707317.American Journal of Respiratory and Critical Care Medicine 10/2014; 190(10). DOI:10.1164/rccm.201405-0967OC · 11.99 Impact Factor
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ABSTRACT: Objective: To assess the performance of QuantiFERON-TB Gold In-Tube (QFT-GIT) test for active tuberculosis (TB) in HIV adults, and its variation over time in patients on antiretroviral therapy (ART) and/or isoniazide preventive therapy (IPT). Methods: Transversal study and cohort nested in the Temprano ANRS 12136 randomized controlled trial assessing benefits of initiating ART earlier than currently recommended by World Health Organization, with or without a 6-month IPT. Performance of QFT-GIT for detecting active TB at baseline in the first 50% participants, and 12-month incidence of conversion/reversion in the first 25% participants were assessed. QFT-GIT threshold for positivity was 0.35 IU/ml. Results: Among the 975 first participants (median baseline CD4 count 383/mm(3), positive QFT-GIT test 35%), 2.7% had active TB at baseline. QFT-GIT sensitivity, specificity, positive and negative predictive value for active TB were 88.0%, 66.6%, 6.5% and 99.5%. For the 444 patients with a second test at 12 months, rates for conversion and reversion were 9.3% and 14%. Reversion was more frequent in patients without ART and younger patients. IPT and early ART were not associated with reversion/conversion. Conclusion: A negative QFT-GIT could rule out active TB in HIV-infected adults not severely immunosuppressed, thus avoiding repeated TB testing and accelerating diagnosis and care for other diseases.PLoS ONE 10/2014; 9(10):e107245. DOI:10.1371/journal.pone.0107245 · 3.53 Impact Factor