Prospective Longitudinal Study Design

This is the first prospective longitudinal study to evaluate whether sputum LAM concentrations measured by PATHFAST-LAM predict clinical treatment outcomes in PTB. The study uses an adaptive design with an initial feasibility cohort of 300 participants, based on an expected poor-outcome rate of approximately 20% and a 15–20% allowance for loss to follow-up. Whole-genome sequencing is performed on baseline and relapse isolates to differentiate true relapse from reinfection. The primary endpoint is the AUC representing the discriminatory performance of sputum LAM changes from baseline to week 4 and/or week 8 for the composite poor outcome. Post-treatment follow-up is limited to 3 months by telephone, so late relapses will not be captured. Cost-effectiveness and feasibility for routine implementation are not formally assessed, as PATHFAST testing is performed by research staff rather than facility staff.