Bedaquiline Resistance In Drug-Resistant Tuberculosis Hiv Co-Infected Patients

Bedaquiline is a highly effective drug for tuberculosis (TB) and is an important part of current regimens for drug-resistant TB. Bedaquiline resistance is rarely tested in operational settings. In a prospective cohort of 292 patients with drug-resistant TB and HIV starting bedaquiline in KwaZulu-Natal, South Africa, we whole genome sequenced isolates from 92 baseline culture positive patients. Five patients were infected with strains harbouring mutations associated with bedaquiline resistance, and an additional five acquired resistance mutations during treatment. Among the baseline culture positive patients, those with baseline or acquired resistance mutations had substantially worse clinical outcomes compared to patients without. Given the importance of bedaquiline in current and future treatment, routine bedaquiline resistance monitoring is urgently needed and programmes require strengthening to ensure full adherence and prevent widespread transmission of bedaquiline-resistant tuberculosis. Footnotes This manuscript has recently been accepted for publication in the European Respiratory Journal . It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article. Conflict of interest: Dr Nimmo reports grants from Wellcome Trust, during the conduct of the study. Conflict of interest: Dr Millard reports grants from Wellcome Trust, during the conduct of the study. Conflict of interest: Dr Brien has nothing to disclose. Conflict of interest: Dr Moodley has nothing to disclose. Conflict of interest: Dr van Dorp has nothing to disclose. Conflict of interest: Dr Lutchminarain has nothing to disclose. Conflict of interest: Dr Wolf reports grants from National Institutes of Health National Institute of Allergy and Infectious Diseases, during the conduct of the study. Conflict of interest: Dr Grant has nothing to disclose. Conflict of interest: Dr Balloux has nothing to disclose. Conflict of interest: Dr Pym reports personal fees from Janssen Pharmaceutica, outside the submitted work. Conflict of interest: Dr PADAYATCHI has nothing to disclose. Conflict of interest: Dr Ou0027Donnell has nothing to disclose.