Mycobacterium avium complex (MAC) elimination slopes from sputum are potential treatment response biomarkers in patients with HIV and pulmonary MAC.

BACKGROUND

Lack of quantitative and reproducible treatment response biomarkers is slowing the development of better therapy regimens for pulmonary Mycobacterium avium complex (P-MAC) disease. We hypothesised that steeper bacterial elimination rate slopes (BERSs) would be associated with faster mycobacterial cure and more favourable outcomes.

METHODS

We retrospectively compared serial sputum culture (SSC) trajectories and outcomes of 29 P-MAC patients, of whom 26/29 (90%) had concurrent HIV infection, treated with guideline-based therapy (GBT) versus non-GBT regimens at a tertiary hospital in Gauteng province of South Africa between 2013 and 2017. We used 'current value' parameterisation of joint models with BERSs as longitudinal biomarkers for the composite outcomes of time-to-death or therapy failure.

RESULTS

Overall, initial bacterial burden and BERS trajectories were heterogeneous. BERSs ranged from -0.034 to 0.013 log10 CFU/mL per day. BERSs were significantly steeper in the 18 (62%) censored survivors, with median (interquartile range) -0.011 (-0.021, -0.008), versus 0.002 (-0.008, 0.003) in 11 (38%) non-survivors or therapy failure. In multivariate analyses, one log10 CFU/mL/day decline was associated with an 88% reduction in the hazard for death or therapy failure (95% confidence intervals, 0.04, 0.34).

CONCLUSION

BERSs from sputum are potential P-MAC treatment response biomarkers, which should be evaluated further in larger prospective studies of people with and without HIV.