title: QuantiFERON conversion following tuberculin administration is common in HIV infection and relates to baseline response.
abstract: BACKGROUND
  HIV-1 infection impairs tuberculosis (TB) specific immune responses affecting the diagnosis of latent TB. We aimed to (1) determine the proportion of HIV-1-infected adults with a negative QuantiFERON®-TB Gold in-tube (QFT-GIT) and Tuberculin skin testing (TST) that convert to QFT-GIT positive following TST, and (2) evaluate the relationship between conversion and baseline QFT-GIT results.
  
  
  METHODS
  HIV-1 infected adults being screened for a TB vaccine study in South Africa underwent QFT-GIT followed by TST. As per protocol, QFT-GIT was repeated if randomization was delayed allowing for evaluation of TST boosting in a proportion of participants.
  
  
  RESULTS
  Of the 22 HIV-1 infected, TST and QFT-GIT negative adults (median CD4 477/mm3IQR 439-621) who had QFT-GIT repeated after median 62 days (IQR 49-70), 40.9 % (95 % CI 18.6-63.2 %) converted. Converters had a significantly greater increase in the background subtracted TB antigen response (TBAg-Nil - all units IU/mL) following TST, 0.82 (IQR 0.39-1.28) vs 0.03 (IQR -0.05-0.06), p = 0.0001. Those who converted also had a significantly higher baseline TBAg-Nil 0.21(IQR 0.17-0.26) vs 0.02(IQR 0.01-0.07), p = 0.002. Converters did not differ with regard to CD4 count or ART status. ROC analysis showed a baseline cut off of 0.15 correctly classified 86.4 % of converters with 88.9 % sensitivity.
  
  
  CONCLUSIONS
  Our findings support the possibility that there are 2 distinct groups in an HIV-1 infected population with negative QFT-GIT and TST; a true negative group and a group showing evidence of a weak Mtb specific immune response that boosts significantly following TST resulting in conversion of the test result that may represent false negatives. Further evaluation of whether a lower cut off may improve sensitivity of QFT-GIT in this population is warranted.
authors.affiliation: Clinical Infectious Diseases Research Initiative, Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, Cape Town, South Africa. hanif.esmail@ndcls.ox.ac.uk.|Department of Medicine, Imperial College London, London, UK. hanif.esmail@ndcls.ox.ac.uk.|Nuffield Division of Clinical and Laboratory Sciences, Radcliffe Department of Medicine, University of Oxford, Oxford, UK. hanif.esmail@ndcls.ox.ac.uk.
authors.forename: Hanif
authors.identifier: http://orcid.org/0000-0002-4278-9316
authors.initials: H
authors.lastname: Esmail
authors.affiliation: Clinical Infectious Diseases Research Initiative, Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, Cape Town, South Africa.|Department of Medicine, University of Cape Town, Cape Town, South Africa.
authors.forename: Friedrich
authors.initials: F
authors.lastname: Thienemann
authors.affiliation: Clinical Infectious Diseases Research Initiative, Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, Cape Town, South Africa.|Division of Public Health Medicine, School of Public Health and Family Medicine, University of Cape Town, Cape Town, South Africa.
authors.forename: Tolu
authors.initials: T
authors.lastname: Oni
authors.affiliation: Clinical Infectious Diseases Research Initiative, Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, Cape Town, South Africa.
authors.forename: Rene
authors.initials: R
authors.lastname: Goliath
authors.affiliation: Clinical Infectious Diseases Research Initiative, Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, Cape Town, South Africa.|The Francis Crick Institute, London, UK.
authors.forename: Katalin A
authors.initials: KA
authors.lastname: Wilkinson
authors.affiliation: Clinical Infectious Diseases Research Initiative, Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, Cape Town, South Africa.|Department of Medicine, Imperial College London, London, UK.|The Francis Crick Institute, London, UK.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Wilkinson
mesh_terms: D017088:AIDS-Related Opportunistic Infections / Q000175:diagnosis / Q000382:microbiology; D000328:Adult; D018791:CD4 Lymphocyte Count; D005260:Female; D015658:HIV Infections / Q000150:complications / Q000382:microbiology*; D006801:Humans; D007159:Immunologic Tests / Q000379:methods*; D055985:Latent Tuberculosis / Q000175:diagnosis* / Q000821:virology; D008297:Male; D012372:ROC Curve; D013019:South Africa; D014374:Tuberculin Test / Q000379:methods; D014376:Tuberculosis / Q000453:epidemiology
keywords: Diagnostics; HIV; Interferon Gamma Release Assay; Latent tuberculosis; QuantiFERON®-TB Gold in-tube