Advances in tuberculosis treatment: novel regimens, new drug pipelines, host-directed therapies, and updated management guidelines.

Tuberculosis treatment has undergone its most profound transformation since the launch of the standardised DOTS strategy in 1994. Since 2020, a series of pivotal randomised trials, including TB-PRACTECAL, ZeNix, Nix-TB, endTB, BEAT-TB, SHINE, and Study 31/A5349, have redefined the management of both drug-susceptible and drug-resistant tuberculosis. These studies have enabled shorter, fully oral regimens with improved efficacy and safety across adult and paediatric populations, including people with HIV, and have driven major updates to WHO treatment guidelines. Despite these advances, tuberculosis remains the leading cause of death from a single infectious agent worldwide, with substantial mortality occurring before treatment initiation due to delayed diagnosis and pretreatment loss to follow-up, and additional deaths during treatment related to advanced disease, drug resistance, comorbidities, and challenges with treatment tolerance and adherence. In 2024, an estimated 10·7 million people developed tuberculosis of whom approximately 390 000 developed multidrug-resistant (MDR) or rifampicin-resistant (RR) tuberculosis. Tuberculosis caused an estimated 1·23 million deaths globally, including approximately 150 000 deaths attributable to MDR tuberculosis or RR tuberculosis. Outcomes remain poorest among people with HIV, young children (who rarely access treatment and prevention), migrants, and displaced populations. The tuberculosis drug development pipeline in 2026 is more advanced than at any time since the introduction of rifampicin. Novel and repurposed compounds, including DprE1 inhibitors, next-generation oxazolidinones (including TBAJ-587 and TBAJ-876), cytochrome bc1 inhibitors, and long-acting formulations, are in late-stage evaluation. Host-directed therapies are also advancing as adjunctive strategies to reduce inflammation-mediated tissue damage and long-term morbidity, although they remain investigational. This Series paper synthesises advances in adult and paediatric tuberculosis therapeutics from Nov 15, 2020, to Jan 15, 2026, and highlights priorities to translate therapeutic innovation into equitable population-level effects.