Advances in tuberculosis treatment: novel regimens, new drug pipelines, host-directed therapies, and updated management guidelines.
Recent trials have led to promising new tuberculosis treatments, but significant challenges remain in reducing mortality and improving access for vulnerable populations.
Where it sits
this study against the rest of the aod-9604 corpusSummary and findings
The paper reviews significant advances in tuberculosis treatment, focusing on novel regimens and drug pipelines from 2020 to 2026. It highlights pivotal trials that have led to shorter, fully oral regimens for both drug-susceptible and drug-resistant tuberculosis. The study also discusses the challenges in treatment adherence and the high mortality rate associated with tuberculosis.
Abstract
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.
Background
Tuberculosis remains the leading cause of death from a single infectious agent, necessitating advancements in treatment regimens. The study addresses the need for improved management of drug-susceptible and drug-resistant tuberculosis, especially in vulnerable populations. Recent trials have aimed to develop shorter, fully oral regimens with better efficacy and safety profiles.
Methods
The paper synthesizes findings from several pivotal randomized trials conducted between 2020 and 2026. These trials, including TB-PRACTECAL and ZeNix, evaluated new treatment regimens for tuberculosis across diverse populations, including adults, children, and people with HIV. The focus was on both drug-susceptible and drug-resistant forms of the disease.
Results
The trials have led to the development of shorter, fully oral regimens that have improved efficacy and safety. However, tuberculosis still causes significant mortality, with 1.23 million deaths globally in 2024. The poorest outcomes are seen in populations such as people with HIV and young children.
Interpretation
While the advances in treatment regimens are promising, the clinical significance is tempered by ongoing challenges such as delayed diagnosis and treatment adherence. The high mortality rate underscores the need for continued innovation and equitable access to treatment. The study highlights the importance of translating these advances into population-level benefits.
Key findings
- 10.7 million people developed tuberculosis in 2024.
- Approximately 390,000 developed multidrug-resistant or rifampicin-resistant tuberculosis in 2024.
- Tuberculosis caused an estimated 1.23 million deaths globally in 2024.
- 150,000 deaths were attributable to MDR or RR tuberculosis in 2024.
- Outcomes are poorest among people with HIV, young children, migrants, and displaced populations.
Limitations
- No specific efficacy or safety data for individual regimens reported.
- Lacks methodological details of the trials discussed.
- Focuses on observational synthesis rather than new experimental data.