Journal
LANCET INFECTIOUS DISEASES
Volume 14, Issue 4, Pages 327-340Publisher
ELSEVIER SCI LTD
DOI: 10.1016/S1473-3099(13)70328-1
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Funding
- UK European Union FP7Rid-RTI programme grant
- European Developing Countries Clinical Trials Partnership TB NEAT
- PanACEA
- REMox grants
- UBS Optimus Foundation, Switzerland
- National Institute for Health Research Biomedical Research Centre, University College London Hospitals, London, UK
- European Community's Seventh Framework Programme [FP7/2007-13, 260872]
- BmBF grants
- European Developing Countries Clinical Trials Partnership PanACEA [2007.32011.013]
- Global Alliance for Tuberculosis Drug Development
- European and Developing Country Clinical Trials Partnership [IP.200732011.011, IP.200732011.012, IP.2007.32011.013]
- European Developing Countries Clinical Trials Partnership
- TB NEAT
- HLF (Heart and Lung foundation) Sweden
- Vetenskapsradet
- VINNOVA
- National Institute of Allergies and Infectious Diseases, National Institutes of Health, Department of Health and Human Services [HHSN272200800014C]
- MRC [MC_U122888469] Funding Source: UKRI
- Medical Research Council [MC_U122888469] Funding Source: researchfish
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About 1.3 million people died of tuberculosis in 2012, despite availability of effective drug treatment. Barriers to improvements in outcomes include long treatment duration (resulting in poor patient adherence and loss of patients to follow-up), complex regimens that involve expensive and toxic drugs, toxic effects when given with antiretroviral therapy, and multidrug resistance. After 50 years of no antituberculosis drug development, a promising pipeline is emerging through the repurposing of old drugs, re-engineering of existing antibacterial compounds, and discovery of new compounds. A range of novel antituberculosis drugs are in preclinical development, several phase 2 and 3 trials are underway, and use of adjunct therapies is being explored for drug-sensitive and drug-resistant tuberculosis. Historical advances include approval of two new drugs, delamanid and bedaquiline. Combinations of new and existing drugs are being assessed to shorten the duration of therapy and to treat multidrug-resistant tuberculosis. There has also been progress in development of new antituberculosis drugs that are active against dormant or persister populations of Mycobacterium tuberculosis. In this Review, we discuss recent advances in antituberculosis drug discovery and development, clinical trial designs, laboratory methods, and adjunct host-directed therapies, and we provide an update of phase 3 trials of various fluoroquinolones (RIFAQUIN, NIRT, OFLOTUB, and REMoxTB). We also emphasise the need to engage the community in design, implementation, and uptake of research, to increase international cooperation between drug developers and health-care providers adopting new regimens.
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