title: The impact of HIV infection and CD4 cell count on the performance of an interferon gamma release assay in patients with pulmonary tuberculosis.
abstract: BACKGROUND
  The performance of the tuberculosis specific Interferon Gamma Release Assays (IGRAs) has not been sufficiently documented in tuberculosis- and HIV-endemic settings. This study evaluated the sensitivity of the QuantiFERON TB-Gold In-Tube (QFT-IT) in patients with culture confirmed pulmonary tuberculosis (PTB) in a TB- and HIV-endemic population and the effect of HIV-infection and CD4 cell count on test performance.
  
  
  RESULTS
  161 patients with sputum culture confirmed PTB were subjected to HIV- and QFT-IT testing and measurement of CD4 cell count. The QFT-IT was positive in 74% (119/161; 95% CI: 67-81%). Sensitivity was higher in HIV-negative (75/93) than in HIV-positive (44/68) patients (81% vs. 65%, p = 0.02) and increased with CD4 cell count in HIV-positive patients (test for trend p = 0.03). 23 patients (14%) had an indeterminate result and this proportion decreased with increasing CD4 cell count in HIV-positive patients (test for trend p = 0.03). Low CD4 cell count (<300 cells/microl) did not account for all QFT-IT indeterminate nor all negative results. Sensitivity when excluding indeterminate results was 86% (95% CI: 81-92%) and did not differ between HIV-negative and HIV-positive patients (88 vs. 83%, p = 0.39).
  
  
  CONCLUSIONS
  Sensitivity of the QFT-IT for diagnosing active PTB infection was reasonable when excluding indeterminate results and in HIV-negative patients. However, since the test missed more than 10% of patients, its potential as a rule-out test for active TB disease is limited. Furthermore, test performance is impaired by low CD4 cell count in HIV-positive patients and possibly by other factors as well in both HIV-positive and HIV-negative patients. This might limit the potential of the test in populations where HIV-infection is prevalent.
authors.affiliation: Department of Infectious Diseases, University of Copenhagen, Rigshospitalet, Copenhagen, Denmark. martine@aabye.com
authors.forename: Martine G
authors.initials: MG
authors.lastname: Aabye
authors.forename: Pernille
authors.initials: P
authors.lastname: Ravn
authors.forename: George
authors.initials: G
authors.lastname: PrayGod
authors.forename: Kidola
authors.initials: K
authors.lastname: Jeremiah
authors.forename: Apolinary
authors.initials: A
authors.lastname: Mugomela
authors.forename: Maria
authors.initials: M
authors.lastname: Jepsen
authors.forename: Daniel
authors.initials: D
authors.lastname: Faurholt
authors.forename: Nyagosya
authors.initials: N
authors.lastname: Range
authors.forename: Henrik
authors.initials: H
authors.lastname: Friis
authors.forename: John
authors.initials: J
authors.lastname: Changalucha
authors.forename: Aase B
authors.initials: AB
authors.lastname: Andersen
mesh_terms: D000328:Adult; D001671:Biochemistry / Q000379:methods; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism*; D005260:Female; D015658:HIV Infections / Q000097:blood* / Q000150:complications*; D006679:HIV Seropositivity; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism*; D008297:Male; D015995:Prevalence; D011933:Reagent Kits, Diagnostic; D012680:Sensitivity and Specificity; D013183:Sputum / Q000378:metabolism; D013636:Tanzania; D014397:Tuberculosis, Pulmonary / Q000097:blood* / Q000150:complications*
chemical_list: D011933:Reagent Kits, Diagnostic; D007371:Interferon-gamma