title: Improved sensitivity of an interferon-gamma release assay (T-SPOT.TB™) in combination with tuberculin skin test for the diagnosis of latent tuberculosis in the presence of HIV co-infection.
abstract: BACKGROUND
  Interferon-gamma release assays (IGRA) are more specific than the tuberculin skin test (TST) for the diagnosis of Mycobacterium tuberculosis infection. Data on sensitivity are controversial in HIV infection.
  
  
  METHODS
  IGRA (T-SPOT.TB) was performed using lymphocytes stored within 6 months before culture-confirmed tuberculosis was diagnosed in HIV-infected individuals in the Swiss HIV Cohort Study.
  
  
  RESULTS
  64 individuals (69% males, 45% of non-white ethnicity, median age 35 years (interquartile range [IQR] 31-42), 28% with prior AIDS) were analysed. Median CD4 cell count was 223 cells/μl (IQR 103-339), HIV-RNA was 4.7 log10 copies/mL (IQR 4.3-5.2). T-SPOT.TB resulted positive in 25 patients (39%), negative in 18 (28%) and indeterminate in 21 (33%), corresponding to a sensitivity of 39% (95% CI 27-51%) if all test results were considered, and 58% (95% CI 43-74%) if indeterminate results were excluded. Sensitivity of IGRA was independent of CD4 cell count (p = 0.698). Among 44 individuals with available TST, 22 (50%) had a positive TST. Agreement between TST and IGRA was 57% (kappa = 0.14, p = 0.177), and in 34% (10/29) both tests were positive. Combining TST and IGRA (at least one test positive) resulted in an improved sensitivity of 67% (95% CI 52-81%). In multivariate analysis, older age was associated with negative results of TST and T-SPOT.TB (OR 3.07, 95% CI 1,22-7.74, p = 0.017, per 10 years older).
  
  
  CONCLUSIONS
  T-SPOT.TB and TST have similar sensitivity to detect latent TB in HIV-infected individuals. Combining TST and IGRA may help clinicians to better select HIV-infected individuals with latent tuberculosis who qualify for preventive treatment.
authors.affiliation: Division of Infectious Diseases and Hospital Epidemiology, University Hospital Basel, Basel, Switzerland.
authors.forename: Luigia
authors.initials: L
authors.lastname: Elzi
authors.forename: Ingrid
authors.initials: I
authors.lastname: Steffen
authors.forename: Hansjakob
authors.initials: H
authors.lastname: Furrer
authors.forename: Jan
authors.initials: J
authors.lastname: Fehr
authors.forename: Matthias
authors.initials: M
authors.lastname: Cavassini
authors.forename: Bernard
authors.initials: B
authors.lastname: Hirschel
authors.forename: Matthias
authors.initials: M
authors.lastname: Hoffmann
authors.forename: Enos
authors.initials: E
authors.lastname: Bernasconi
authors.forename: Stefano
authors.initials: S
authors.lastname: Bassetti
authors.forename: Manuel
authors.initials: M
authors.lastname: Battegay
mesh_terms: D000328:Adult; D019411:Clinical Laboratory Techniques / Q000379:methods*; D015331:Cohort Studies; D005260:Female; D015658:HIV Infections / Q000150:complications*; D006801:Humans; D059425:Interferon-gamma Release Tests / Q000379:methods*; D055985:Latent Tuberculosis / Q000175:diagnosis*; D008297:Male; D009169:Mycobacterium tuberculosis / Q000276:immunology; D012680:Sensitivity and Specificity; D013557:Switzerland; D014374:Tuberculin Test / Q000379:methods*
references.citation: Gut. 2010 Sep;59(9):1252-8
references.pmid: 20660698
references.citation: Eur Respir J. 2010 Sep;36(3):594-600
references.pmid: 20075047
references.citation: MMWR Recomm Rep. 1992 Dec 18;41(RR-17):1-19
references.pmid: 1361652
references.citation: Int J Tuberc Lung Dis. 2008 Apr;12(4):417-23
references.pmid: 18371268
references.citation: PLoS One. 2008 Jun 18;3(6):e2489
references.pmid: 18560573
references.citation: MMWR Recomm Rep. 2005 Dec 16;54(RR-15):49-55
references.pmid: 16357824
references.citation: PLoS One. 2009;4(1):e4220
references.pmid: 19156218
references.citation: Tuberculosis (Edinb). 2011 May;91(3):260-7
references.pmid: 21459676
references.citation: Am J Respir Crit Care Med. 2007 Apr 1;175(7):737-42
references.pmid: 17218620
references.citation: Arch Intern Med. 2003 May 12;163(9):1009-21
references.pmid: 12742798
references.citation: J Virol. 2009 May;83(9):4404-11
references.pmid: 19211737
references.citation: AIDS. 2008 Nov 30;22(18):2471-9
references.pmid: 19005270
references.citation: East Afr Med J. 2008 Sep;85(9):442-9
references.pmid: 19537417
references.citation: Clin Infect Dis. 1993 Dec;17(6):968-75
references.pmid: 8110954
references.citation: PLoS Med. 2007 Mar 27;4(3):e96
references.pmid: 17388662
references.citation: Lancet. 2006 Mar 18;367(9514):938-40
references.pmid: 16546542
references.citation: N Engl J Med. 1999 Feb 4;340(5):367-73
references.pmid: 9929528
references.citation: JAMA. 2002 Feb 27;287(8):996-1002
references.pmid: 11866647
references.citation: Clin Exp Immunol. 2007 Oct;150(1):91-8
references.pmid: 17680823
references.citation: Int J Tuberc Lung Dis. 2007 Nov;11(11):1190-5
references.pmid: 17958980
references.citation: AIDS. 2002 Nov 22;16(17):2285-93
references.pmid: 12441800
references.citation: Ann Intern Med. 2008 Aug 5;149(3):177-84
references.pmid: 18593687
references.citation: MMWR Recomm Rep. 2010 Jun 25;59(RR-5):1-25
references.pmid: 20577159
references.citation: Am J Respir Crit Care Med. 2007 Mar 1;175(5):514-20
references.pmid: 17158278
references.citation: JAMA. 2000 Apr 19;283(15):2003-7
references.pmid: 10789669
references.citation: PLoS One. 2010 Sep 07;5(9):e12577
references.pmid: 20830287
references.citation: BMC Infect Dis. 2009 Feb 10;9:15
references.pmid: 19208218
references.citation: Lancet. 2004 Dec 18-31;364(9452):2196-203
references.pmid: 15610806
references.citation: Respir Res. 2006 Apr 01;7:56
references.pmid: 16579856
references.citation: Am J Respir Crit Care Med. 2004 Jul 1;170(1):59-64
references.pmid: 15059788
references.citation: Lancet. 2006 Apr 22;367(9519):1328-34
references.pmid: 16631911
references.citation: N Engl J Med. 2004 May 13;350(20):2060-7
references.pmid: 15141044
references.citation: Clin Infect Dis. 2007 Jan 1;44(1):94-102
references.pmid: 17143823
references.citation: BMJ. 1995 Dec 2;311(7018):1468-71
references.pmid: 8520334
references.citation: Int J Epidemiol. 2010 Oct;39(5):1179-89
references.pmid: 19948780
references.citation: Chest. 2009 Jul;136(1):198-204
references.pmid: 19318676
references.citation: PLoS One. 2008 Jan 16;3(1):e1441
references.pmid: 18197251
references.citation: Int J Infect Dis. 2008 Nov;12(6):645-52
references.pmid: 18534887