Dynamics of Quantiferon-Gold Plus results in a large TB preventive treatment trial across three high-burden HIV/TB countries.

Abstract

We report the longitudinal analysis of QuantiFERON-Gold Plus (QFT-plus) results from a clinical trial conducted in three high TB/HIV burden countries, comparing three different tuberculosis preventive treatment (TPT) regimens in people living with HIV (PLHIV). PLHIV were enrolled in Ethiopia, Mozambique and South Africa, and randomised to: (i) one course of weekly rifapentine-isoniazid for 3 months (3HP); (ii) weekly rifapentine-isoniazid for 3 months given annually for 2 years (p3HP); (iii) daily isoniazid for 6 months (6H). QFT-plus testing was performed at baseline, M12 and M24. Quantitative and qualitative results, and serial changes (conversions and reversions) were assessed. From baseline to M12, 13.0% (196/1502) of participants converted, with no differences between 3HP (13.1%) and 6H (12.9%). From M12 to M24 conversion occurred in 4.0% of participants receiving p3HP and 9.4% of those receiving 3HP (p-value 0.110). 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 QFT-plus positive at baseline (aHR, 1.66; 95% CI, 1.41-1.89, p-value = 0.034). QFT-Plus conversions and reversions occurred frequently in PLHIV 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 IGRA results in PLHIV in high-transmission scenarios.