title: Predictive value of interferon-gamma release assays for postpartum active tuberculosis in HIV-1-infected women.
abstract: BACKGROUND
  Data on the prognostic utility of interferon-gamma release assays (IGRAs) for active tuberculosis (TB) among human immunodeficiency virus 1 (HIV-1) infected individuals are limited.
  
  
  METHODS
  Samples from a perinatal cohort of HIV-1-infected women in Kenya, obtained during pregnancy, were tested using T-SPOT®.TB IGRAs to detect Mycobacterium tuberculosis-specific interferon-gamma (IFN-γ) responses. IFN-γ (cut-off values of >0, ≥6 and ≥10 spot-forming cells [SFC]/well) and CD4 cell count (cut-off values of <250 and <350 cells/l) were evaluated to determine sensitivity and specificity using a time-dependent receiver operating characteristic curve and positive predictive value (PPV) using the Kaplan Meier method for future TB within 1 year postpartum.
  
  
  RESULTS
  Of 327 women, 9 developed TB within 1 year postpartum (incidence rate 3.5/100 person-years of follow-up, 95%CI 1.66.7). IFN-γ ≥ 6 SFC/well was associated with an optimal trade-off between sensitivity (78%) and specificity (55%) and a PPV of 5.9%. In women with CD4 cell count of <250 cells/μl, the sensitivity and specificity of IFN- 6 SFC/well were respectively 89% and 63%, and the PPV was 19.2%.
  
  
  CONCLUSIONS
  Among HIV-1 infected women, IFN-γ response (≥6 SFC/well) during pregnancy lacked a high PPV for postpartum TB, but had higher sensitivity and PPV among immunosuppressed women (CD4 cell count of <250 cells/μl).
authors.affiliation: Department of Epidemiology, University of Washington, Seattle, Washington, USA.
authors.forename: S R
authors.initials: SR
authors.lastname: Jonnalagadda
authors.forename: E
authors.initials: E
authors.lastname: Brown
authors.forename: B
authors.initials: B
authors.lastname: Lohman-Payne
authors.forename: D
authors.initials: D
authors.lastname: Wamalwa
authors.forename: C
authors.initials: C
authors.lastname: Farquhar
authors.forename: G C
authors.initials: GC
authors.lastname: John-Stewart
mesh_terms: D019540:Area Under Curve; D015415:Biomarkers / Q000378:metabolism; D018791:CD4 Lymphocyte Count; D060085:Coinfection; D005260:Female; D015658:HIV Infections / Q000175:diagnosis / Q000453:epidemiology / Q000276:immunology / Q000821:virology*; D015497:HIV-1 / Q000302:isolation & purification*; D006801:Humans; D015994:Incidence; D007371:Interferon-gamma / Q000378:metabolism*; D059425:Interferon-gamma Release Tests; D053208:Kaplan-Meier Estimate; D007630:Kenya / Q000453:epidemiology; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D049590:Postpartum Period; D011237:Predictive Value of Tests; D011247:Pregnancy; D012372:ROC Curve; D013997:Time Factors; D014376:Tuberculosis / Q000175:diagnosis* / Q000453:epidemiology / Q000276:immunology / Q000382:microbiology
chemical_list: D015415:Biomarkers; C573415:IFNG protein, human; D007371:Interferon-gamma