Dynamics of QuantiFERON-TB Gold Plus Results in a Large TB Preventive Treatment Trial Across 3 High-Burden HIV/TB...

We report the longitudinal analysis of QuantiFERON-TB Gold Plus (QFT-Plus) results from a clinical trial conducted in 3 countries with a high tuberculosis (TB)/human immunodeficiency virus (HIV) burden, comparing 3 different TB preventive treatment (TPT) regimens in people with HIV (PWH).

PWH were enrolled in Ethiopia, Mozambique, and South Africa and randomized to (i) 1 course of weekly rifapentine-isoniazid for 3 months (3HP), (ii) weekly rifapentine-isoniazid for 3 months given annually for 2 years (p3HP), or (iii) daily isoniazid for 6 months (6H). QFT-Plus testing was performed at baseline, month 12, and month 24. Quantitative and qualitative results, and serial changes (conversions and reversions) were assessed.

From baseline to month 12, 13.0% (196/1502) of participants converted, with no differences between 3HP (13.1%) and 6H (12.9%). From month 12 to month 24, conversion occurred in 4.0% of participants receiving a second course of 3HP (p3HP arm), and in 9.4% of those not receiving a second course (3HP) (P = .110). Overall reversions occurred in 19.0% (178/935) of participants. Reversion rates were similar across study arms and timepoints. The risk of developing TB during the study period was higher among individuals who were QFT-Plus positive at baseline (adjusted hazard ratio, 1.66 [95% confidence interval, 1.41-1.89], P = .034).

QFT-Plus conversions and reversions occurred frequently in PWH and did not differ by TPT regimen or between those who did and did not receive a second course of TPT. The high rate of QFT positivity, along with the large proportion of conversions despite TPT, highlights the complexity of interpreting serial interferon-gamma release assay results in PWH in high-transmission scenarios.