title: Principles for designing future regimens for multidrug-resistant tuberculosis.
abstract: Fewer than 20% of patients with multidrug-resistant (MDR) tuberculosis are receiving treatment and there is an urgent need to scale up treatment programmes. One of the biggest barriers to scale-up is the treatment regimen, which is lengthy, complex, ineffective, poorly tolerated and expensive. For the first time in over 50 years, new drugs have been developed specifically to treat tuberculosis, with bedaquiline and potentially delamanid expected to be available soon for treatment of MDR cases. However, if the new drugs are merely added to the current treatment regimen, the new regimen will be at least as lengthy, cumbersome and toxic as the existing one. There is an urgent need for strategy and evidence on how to maximize the potential of the new drugs to improve outcomes and shorten treatment. We devised eight key principles for designing future treatment regimens to ensure that, once they are proven safe in clinical trials, they will be clinically effective and programmatically practicable. Regimens should contain at least one new class of drug; be broadly applicable for use against MDR and extensively drug-resistant Mycobacterium tuberculosis complex strains; contain three to five effective drugs, each from a different drug class; be delivered orally; have a simple dosing schedule; have a good side-effect profile that allows limited monitoring; last a maximum of 6 months; and have minimal interaction with antiretrovirals. Following these principles will maximize the potential of new compounds and help to overcome the clinical and programmatic disadvantages and scale-up constraints that plague the current regimen.
authors.affiliation: Access Campaign, Médecins Sans Frontières, 78 Rue de Lausanne, PO Box 116, Geneva, CH1211, Switzerland .
authors.forename: Grania
authors.initials: G
authors.lastname: Brigden
authors.affiliation: Médecins Sans Frontières, London, England .
authors.forename: Bern-Thomas
authors.initials: BT
authors.lastname: Nyang'wa
authors.affiliation: Médecins Sans Frontières, London, England .
authors.forename: Philipp
authors.initials: P
authors.lastname: du Cros
authors.affiliation: Médecins Sans Frontières, Paris, France .
authors.forename: Francis
authors.initials: F
authors.lastname: Varaine
authors.affiliation: Médecins Sans Frontières, Cape Town, South Africa .
authors.forename: Jennifer
authors.initials: J
authors.lastname: Hughes
authors.affiliation: Partners in Health, Boston, United States of America (USA).
authors.forename: Michael
authors.initials: M
authors.lastname: Rich
authors.affiliation: Boston University School of Public Health, Boston, USA .
authors.forename: C Robert
authors.initials: CR
authors.lastname: Horsburgh
authors.affiliation: Department of Global Health and Social Medicine, Harvard Medical School, Boston, USA .
authors.forename: Carole D
authors.initials: CD
authors.lastname: Mitnick
authors.affiliation: Center for Tuberculosis Research, Johns Hopkins University, Baltimore, USA .
authors.forename: Eric
authors.initials: E
authors.lastname: Nuermberger
authors.affiliation: Division of Clinical Pharmacology, University of Cape Town, Cape Town, South Africa .
authors.forename: Helen
authors.initials: H
authors.lastname: McIlleron
authors.affiliation: Medical Research Council Clinical Trials Unit, London, England .
authors.forename: Patrick P J
authors.initials: PP
authors.lastname: Phillips
authors.affiliation: Access Campaign, Médecins Sans Frontières, 78 Rue de Lausanne, PO Box 116, Geneva, CH1211, Switzerland .
authors.forename: Manica
authors.initials: M
authors.lastname: Balasegaram
mesh_terms: D000995:Antitubercular Agents / Q000009:adverse effects / Q000191:economics / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D064687:Diarylquinolines / Q000009:adverse effects / Q000191:economics / Q000627:therapeutic use; D017277:Drug Approval; D015195:Drug Design; D024901:Drug Resistance, Multiple, Bacterial / Q000187:drug effects; D006801:Humans; D009169:Mycobacterium tuberculosis / Q000187:drug effects*; D009593:Nitroimidazoles / Q000009:adverse effects / Q000191:economics / Q000627:therapeutic use; D010080:Oxazoles / Q000009:adverse effects / Q000191:economics / Q000627:therapeutic use; D018088:Tuberculosis, Multidrug-Resistant / Q000188:drug therapy* / Q000453:epidemiology
chemical_list: D000995:Antitubercular Agents; D064687:Diarylquinolines; D009593:Nitroimidazoles; C516022:OPC-67683; D010080:Oxazoles; C493870:bedaquiline