Strategies for shortening tuberculosis therapy

In the absence of effective patient-stratification approaches, tuberculosis (TB) treatment relies on overtreating most patients to ensure high cure rates. Shortening treatment duration without compromising efficacy is therefore high on the agenda of the global TB community. While new and better drugs are certainly needed, we argue that innovative but rational treatment strategies, using both new and existing therapies, will help achieve this goal. There is growing recognition that patient stratification, based on host and pathogen factors, is key to delivering the right drug regimen for the right duration. In this Perspective, we review the current knowledge on the heterogeneity of TB disease and propose approaches to optimize treatment duration in distinct patient groups, taking into consideration the realities of TB control globally. We emphasize key insights that improve the understanding of bacterial vulnerabilities in patients with easy-to-treat and hard-to-treat TB, helping to reduce diagnostic uncertainties. We explore how the TB research community can integrate disease biology, pathology and symptoms, to rethink therapeutic strategies and reduce TB treatment duration.