title: Effect of isoniazid therapy for latent TB infection on QuantiFERON-TB gold in-tube responses in adults with positive tuberculin skin test results in a high TB incidence area: a controlled study.
abstract: BACKGROUND
  T-cell interferon-γ release assays (IGRAs) are used in the diagnosis of Mycobacterium tuberculosis infection and could be useful biomarkers of response to treatment of latent TB infection for clinical trials, infection control units, and TB programs.
  
  
  METHODS
  This investigation was a prospective, controlled substudy of IGRA responses in 82 healthy South African adults with HIV seronegative and positive tuberculin skin test results randomly assigned to treatment with 6 months of daily isoniazid preventive therapy (IPT) or observation before Bacillus Calmette-Guérin revaccination in a clinical trial. QuantiFERON-TB Gold In-Tube (QFT-GIT) assay was used to measure interferon-γ (IFN-γ) response to mycobacterial antigens at baseline and after IPT or observation.
  
  
  RESULTS
  IFN-γ levels declined between baseline and the end of IPT (signed rank test P≤.0001) and between baseline and a similar period of observation without IPT (signed rank test P=.03). The rate of decrease in IFN-γ responses over time did not differ between the groups (Mann-Whitney-Wilcoxon test P=.31). QFT-GIT test results in two subjects (5%) in the IPT group and two subjects (5%) in the observation group reverted from positive to negative during follow-up. No significant difference was found between the groups with respect to baseline positivity or the proportion of patients whose tests reverted to negative.
  
  
  CONCLUSIONS
  IPT had no effect on changes in QFT-GIT readouts during short-term follow-up of adults with positive tuberculin skin tests in a high TB incidence setting. QFT-GIT is unlikely to be a useful biomarker of response to treatment of latent TB infection.
  
  
  BACKGROUND
  ClinicalTrials.gov; No.: NCT01119521; URL: www.clinicaltrials.gov.
authors.forename: John L
authors.initials: JL
authors.lastname: Johnson
authors.forename: Hendrik
authors.initials: H
authors.lastname: Geldenhuys
authors.forename: Bonnie A
authors.initials: BA
authors.lastname: Thiel
authors.forename: Asma
authors.initials: A
authors.lastname: Toefy
authors.forename: Sara
authors.initials: S
authors.lastname: Suliman
authors.forename: Bernadette
authors.initials: B
authors.lastname: Pienaar
authors.forename: Phalkun
authors.initials: P
authors.lastname: Chheng
authors.forename: Thomas
authors.initials: T
authors.lastname: Scriba
authors.forename: W Henry
authors.initials: WH
authors.lastname: Boom
authors.forename: Willem
authors.initials: W
authors.lastname: Hanekom
authors.forename: Mark
authors.initials: M
authors.lastname: Hatherill
mesh_terms: D000293:Adolescent; D000328:Adult; D000995:Antitubercular Agents / Q000627:therapeutic use; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D007371:Interferon-gamma / Q000276:immunology*; D059425:Interferon-gamma Release Tests / Q000379:methods; D007538:Isoniazid / Q000627:therapeutic use*; D008297:Male; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D011446:Prospective Studies; D013019:South Africa / Q000453:epidemiology; D013997:Time Factors; D016896:Treatment Outcome; D014374:Tuberculin Test / Q000379:methods*; D014376:Tuberculosis / Q000175:diagnosis / Q000453:epidemiology / Q000517:prevention & control*; D055815:Young Adult
chemical_list: D000995:Antitubercular Agents; D007371:Interferon-gamma; D007538:Isoniazid