Abstract

Background Appropriate markers to reflect TB treatment responses are urgently needed mainly for patient care and their application in clinical trials. Additionally, more potent drug combinations in search for treatment shortening regimen are warranted. This work reports results of the TB treatment study PanACEA MAMS TB 01, with nested evaluation of the Molecular Bacterial Load Assay (MBLA) for its potential use as a marker to determine treatment success within a research setting. Methods This study was nested within the multiple‐arm, multiple‐stage (MAMS), phase 2 clinical trial that contributed data set to the PanACEA Biomarkers Expansion programme (PANBIOME) study. Eligible patients were randomised to either the control arm or one of four experimental arms. Culture and MBLA were performed at baseline through to treatment completion comparatively. Results High dose rifampicin at 35mg/kg (RIF35HZE) was superior to control [Hazard ratio 1•46, 95% CI (1•02, 2•11)], p=0•04 for time to culture conversion to negative in MGIT at week 12, the primary endpoint. MBLA had the highest (19%) positive rates compared to MGIT (1.7%) and LJ (1.2%) media at week 26. The median time to negative culture was 35, 55 and 97 days on LJ, MGIT and MBLA respectively. Among the contaminated samples on MGIT and LJ media, MBLA reported 50.9% and 36.3 % as negative respectively. Furthermore, quantitative bacterial load measurements in MBLA and MGIT were significantly correlated (p<0.001). Conclusion A high dose of rifampicin showed superior efficacy in both MGIT and MBLA compared to the control regimen. MBLA as a marker to determine treatment success bears potentials that could contribute in routine patient care and trial setting. However, evaluation on its implementation in routine care and its usefulness as an end point in trials merit consideration.