INT J TUBERC LUNG DIS 17(7):909–916 © 2013 The Union http://dx.doi.org/10.5588/ijtld.12.0927 Changes in QuantiFERON ® -TB Gold In-Tube results during treatment for tuberculous infection M. L. Bastos,* † D. Menzies, ‡ M. T. C. T. Belo,* †§ E. G. Teixeira,* †§ S. T. de Abreu, ¶ P. R. Z. Antas, # A. Trajman* †‡ * Medical School and Post-Graduate Health Education Program, Gama Filho University, Rio de Janeiro, Rio de Janeiro, † Tuberculosis Scientific League, Rio de Janeiro, Rio de Janeiro, Brazil; ‡ Respiratory Epidemiology and Clinical Research Unit, Montreal Chest Institute, McGill University, Montreal, Quebec, Canada; § Medical School, Souza Marques Foundation, Rio de Janeiro, Rio de Janeiro, ¶ Paschoal Granato Laboratory, Rio de Janeiro, Rio de Janeiro, # Clinical Immunology Laboratory, Oswaldo Cruz Institute, Fiocruz, Rio de Janeiro, Rio de Janeiro, Brazil Correspondence to: Anete Trajman, Medical School and Health Education, Gama Filho University, Rua Macedo Sobrinho 74/203, Humaitá 22271-080, Rio de Janeiro, Rio de Janeiro, Brazil. Fax: (+552) 1 2539 9194. e-mail: atrajman@ gmail.com Article submitted 4 December 2012. Final version accepted 21 February 2013. SETTING: Randomised trial comparing 9 months of isoniazid with 4 months of rifampicin for the treatment of high-risk tuberculin skin test positive subjects in Rio de Janeiro, Brazil. OBJECTIVES: To compare QuantiFERON ® -TB Gold In- Tube (QFT-GIT) responses before and 1, 4 and 9 months after starting treatment for latent tuberculous infection (LTBI) according to adherence to one of the two regimens. DESIGN: Participants in the trial were invited to under- go serial QFT-GIT. Within-subject differences at differ- ent time points were analysed as quantitative responses and categorised as positive or negative using different cut-off points. RESULTS: Of 215 participants, 118 completed treat- ment, of whom 58 underwent all three tests; and 97 did not complete treatment, of whom 10 underwent all tests. After 1 month of treatment, there was no significant dif- ference in QFT-GIT response between the groups. After 4 and 9 months, reversions were more frequent in non- adherent subjects. Marked within-subject fluctuations were observed. No cut-off point could be established at which QFT-GIT responses were consistently positive or associated with adherence or type of treatment. CONCLUSION: Frequent within-subject variability in QFT-GIT responses, not associated with LTBI treatment, makes it difficult for clinicians to interpret QFT-GIT conversions and reversions. KEY WORDS: biomarker; interferon-gamma assay; serial testing; latent tuberculosis INTERFERON-GAMMA (IFN-γ) release assays are increasingly used for the diagnosis of latent tubercu- lous infection (LTBI). 1 IFN-γ release assays (IGRAs) have operational characteristics that should be ideal for serial testing: they require only a single visit to give a sample, should be free from observer bias in reading results and provide quantitative results with a single manufacturer-defned cut-off point for a pos- itive test. Unlike the tuberculin skin test (TST), they are ex vivo tests; there is thus no antigen adminis- tered to sensitise individuals and affect subsequent tests through boosting of anamnestic responses. However, several studies have reported unexplained variability in IGRA tests, with high rates of rever- sions and conversions on serial testing. 2–7 Some vari- ability of IGRA response may refect differences in time between blood collection and incubation in the lots of the commercialised kits or in the laboratories where tests were performed. 6,8–10 IFN-γ responses can decline, 11–16 increase or remain stable 17–23 after treatment for LTBI and active TB. IGRA reversions are more frequent when initial results are just above the manufacturer’s suggested threshold or if a con- comitantly performed TST is negative. 2–6,11 The rate of IGRA conversions has been shown to depend on the defnitions used for conversion. 3–6,24 Authors of these studies have suggested that, as for the TST, the ideal IGRA cut-off point value might vary depending on the clinical situation. 2–6,24 In contrast to early biomarkers of successful anti- tuberculosis treatment, such as 2-month sputum con- version, 25–27 there are no validated biomarkers of suc- cessful LTBI treatment. 28 Such biomarkers would be very useful for individual treatment, and would also facilitate trials of alternative LTBI regimens, which at present require lengthy follow-up of large numbers of treated persons, as progression to TB is the only measure of effectiveness. The aim of the present study was to analyse the ef- fect of LTBI treatment on early and late responses to SUMMARY