Bedaquiline resistance in drug-resistant tuberculosis HIV co-infected patients

Camus Nimmo, James Millard, Kayleen Brien, Sashen Moodley, Lucy van Dorp, Keeren Lutchminarain, Allison Wolf, Alison D Grant, Francois Balloux, Alexander S Pym, Nesri Padayatchi, Max O'Donnell, Camus Nimmo, James Millard, Kayleen Brien, Sashen Moodley, Lucy van Dorp, Keeren Lutchminarain, Allison Wolf, Alison D Grant, Francois Balloux, Alexander S Pym, Nesri Padayatchi, Max O'Donnell

Abstract

Genetic mutations linked to bedaquiline resistance were found before starting treatment and acquired during treatment in patients with drug-resistant TB and HIV in KwaZulu-Natal, South Africa. Routine bedaquiline resistance testing needs to be accelerated. http://bit.ly/2vnL4VY

Conflict of interest statement

Conflict of interest: C. Nimmo reports grants (203583/Z/16/Z) from Wellcome Trust, during the conduct of the study. Conflict of interest: J. Millard reports grants (203919/Z/16/Z) from Wellcome Trust, during the conduct of the study. Conflict of interest: K. Brien has nothing to disclose. Conflict of interest: S. Moodley has nothing to disclose. Conflict of interest: L. van Dorp has nothing to disclose. Conflict of interest: K. Lutchminarain has nothing to disclose. Conflict of interest: A. Wolf reports grants from National Institutes of Health National Institute of Allergy and Infectious Diseases, during the conduct of the study. Conflict of interest: A.D. Grant has nothing to disclose. Conflict of interest: F. Balloux has nothing to disclose. Conflict of interest: A.S. Pym is an employee of Janssen Pharmaceutica. Conflict of interest: N. Padayatchi has nothing to disclose. Conflict of interest: M. O'Donnell has nothing to disclose.

Figures

FIGURE 1
FIGURE 1
a) Patients with Rv0678 mutations in positive tuberculosis (TB) sputum cultures. Resistance profiles are for the current and most recent previous TB episodes. Drugs used in treatment regimen are indicated, with those ineffective due to resistance coloured red. H: isoniazid; Z: pyrazinamide; E: ethambutol; FQ: fluoroquinolones; B: bedaquiline; C: clofazimine; Et: ethionamide; L: linezolid; T: terizidone; PAS: p-aminosalicylic acid; D: delamanid; Im: imipenem; RAV: resistance-associated variant; XDR: extensively drug resistant; RR: rifampicin resistant. Patient A was phenotypically ethionamide resistant in the absence of ethionamide resistance-associated variants. Rv0678 variants are categorised as baseline (orange background) or emergent (white background). Amino acid changes at variant sites are specified (fs, frameshift mutation). Bars indicate culture-positive samples without variants (grey), heterozygous variants (light blue) and fixed variants (dark blue). Minimum inhibitory concentrations (MICs) are shown at baseline and at subsequent time-point if performed (red lines). #: in patient J, six further low-frequency Rv0678 variants appeared at 6 months (A57E, R72 T, D88fs, D88A, G121R, L122P). b) Kaplan–Meier curve for survival probability following initiation of bedaquiline therapy with censoring for loss to follow-up. Shaded area indicates 95% confidence interval.

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