Can IGRA Become Negative After Tuberculosis Preventive Therapy?
IGRA tests generally do not become negative after tuberculosis preventive therapy (TPT), and should not be used to monitor treatment response or confirm treatment success. 1, 2
Evidence on IGRA Changes After TPT
Limited Conversion to Negative
The most robust evidence demonstrates that the vast majority of patients remain IGRA-positive after completing preventive therapy:
In a controlled study, 87.5% of patients remained QFT-positive at 3 months post-treatment and 84.6% remained positive at 15 months, with no significant change in IFN-γ levels (mean 6.13 IU/ml at baseline vs. 5.65 IU/ml at 3 and 15 months) 1
A randomized controlled trial in South African adults found that 6 months of isoniazid preventive therapy had no effect on QFT-GIT responses, with only 5% of treated patients reverting to negative—the same rate as the untreated observation group 2
IFN-γ levels declined similarly in both treated and untreated groups over time, indicating that any observed changes were due to natural test variability rather than treatment effect 2
Why IGRA Remains Positive
Test Variability vs. True Treatment Effect
The changes observed in IGRA results after TPT are primarily due to inherent test variability rather than successful eradication of latent infection:
IGRAs have significant intrasubject variability, with discordance rates of 8% for QFT between first and second tests, and 4-22% for T-SPOT depending on response strength 3
Results near the cutoff threshold are particularly prone to spurious changes from positive to negative or vice versa 3
Frequent conversions and reversions occur during serial testing, with fluctuations largely unexplained and nonspecific rather than reflecting true changes in infection status 3
Clinical Implications
Do Not Use IGRA to Monitor Treatment
IGRA should not be used as a biomarker of treatment response for latent TB infection 1, 2:
- The test lacks sensitivity to detect treatment-induced changes in immune responses
- Persistent positivity does not indicate treatment failure
- Conversion to negative does not confirm treatment success
Understanding Test Limitations
Be aware of these critical caveats when interpreting IGRA results in the context of TPT 3:
- Natural test variability can cause conversions and reversions unrelated to treatment
- Values at or near the cutoff should be interpreted with extreme caution
- The criteria for interpreting IGRA changes that identify new infections or treatment response remain uncertain
- An association between IGRA conversion/reversion and subsequent disease risk has not been demonstrated
When Repeat Testing Might Occur
While not recommended for monitoring treatment, repeat IGRA testing may be considered in specific scenarios 3:
- When initial results are indeterminate, borderline, or invalid
- In high-risk individuals (HIV-positive, children <5 years) when initial test is negative to increase sensitivity
- In low-risk individuals when initial test is positive to increase specificity and reduce false-positive diagnoses
The bottom line: A positive IGRA before treatment will almost certainly remain positive after treatment, and this persistent positivity should not influence clinical decision-making about treatment completion or success.