Article Figures & Data
Figures
- Fig 1
Patient disposition and culture status. All 47 randomized patients were analyzed for safety. For the efficacy analysis, 44 patients were available: 2 subjects (one in each group) were diagnosed with XDR TB on a sputum sample submitted before enrollment and were withdrawn within 2 weeks of randomization, and 1 subject in the bedaquiline group remained culture negative at baseline.
- Fig 2
Proportion of patients with positive sputum cultures and time to conversion. (A) Culture conversion over 24 weeks among subjects who discontinued during the first 24 weeks carried forward as not converting (hazard ratio, 2.253; 95% CI, 1.08 to 4.71; P = 0.031). In the bedaquiline (orange line, above) and placebo (blue line, below) groups, the times to 50% culture conversion were 78 and 129 days, respectively, and 17/21 (81.0%) and 15/23 (65.2%) of the subjects, respectively, submitted negative sputum samples at week 24. (B) Culture conversion over 24 weeks among subjects who discontinued scored according to their culture status at the time of discontinuation and kept in the analysis (hazard ratio, 3.135; 95% CI, 1.51 to 6.53; P = 0.002). In the bedaquiline (orange line, above) and placebo (blue line, below) groups, the times to 50% culture conversion were 68 and 126 days, respectively, and 19/21 (90.5%) and 16/23 (69.6%) of the subjects, respectively, were culture negative at week 24 or at the time of discontinuation.
Tables
- Table 1
HIV status, chest radiography findings, drug resistance, and culture status at baseline, 8 weeks, 24 weeks and 104 weeksa
Treatment group and patient Baseline 8 wk 24 wk 104 wk HIV CXR Drug resistance profile Bedaquiline MIC (μg/ml) Culture status Acquired resistance Culture status Acquired resistance Culture status Acquired resistance Bedaquiline + BR group 1 P UC HR 0.06 C– C– –/Dis 24w 2 N UC HRS 0.03 C+ NG C– C–/Com 3 N UC HRZ 0.03 C– C– C–/Com 4 N UC HRSE 0.008 C– –/Dis 17w –/Dis 17w 5 N UC HRSE 0.03 C– C– C–/Com 6 N NC HRZS 0.01 C– C– C+/Com 7 N NC HRZS 0.008 –/Dis 3w –/Dis 3w –/Dis 3w 8 N BC HRSE 0.03 C– C– –/Dis 36w 9 P UC HRSE 0.06 C+ NG C– C–/Com 10 N UC HRZSE 0.06 C– C– –/Dis 26w 11 N UC HRZSE 0.06 C+ NG C– C–/Com 12 N BC HRSE 0.01 C– C– C–/Com 13 P BC HRZSEEth 0.25 C– C– C–/Com 14 N UC HRZSE 0.25 – –/Dis 2w –/Dis 2w 15 N UC HRSEOZ 0.01 C– C– C–/Com 16 N BC HRZSEEth 0.03 C+ K, C C– C+/Com 17 N BC HRZSEK 0.06 C– C– –/Dis 93w 18 N UC NG NG C+ NS C– –/Dis 41w 19 N NC NG 0.03 C+ at 7w NG C– C–/Com 20 N UC NG 0.01 C+ NS C– C–/Com 21 N BC NG NG C– –/Dis 14w –/Dis 14w 22* N UC HRZSEOKC 0.01 –/Dis 2w –/Dis 2w –/Dis 2w 23** N UC NG NG C– C– C–/Com Placebo + BR group 1 N UC HR 0.01 C– –/Dis 10w –/Dis 10w 2 N UC HR 0.03 C– C– C–/Com 3 P UC HR 0.24 C+ No C– C–/Com 4 N UC HRES 0.03 C+ Z, E reverted C– C–/Com 5 N BC HRS 0.01 C– C– C–/Com 6 N UC HRZ 0.03 C+ NS –/Dis 16w –/Dis 16w 7 N UC HRES 0.008 C– –/Dis 16w –/Dis 16w 8 N BC HRZS 0.008 C+ E C+ E, O –/Dis 49w 9 N NC HRZE 0.01 C+ E reverted C– –/Dis 63w C+ at 60w: O, S 10 N UC HRZK 0.06 C+ O, E, S C+ NG –/Dis 63w 11 N BC HRZS 0.01 C+ NG C– –/Dis 47w 12 N UC HRZSE 0.12 C+ O C– C–/Com 13 N BC HRZSE 0.03 C+ NS C– C–/Com 14 N UC HRZSE 0.06 C+ No –/Dis 11w –/Dis 11w 15 N UC HRZSE 0.06 C+ No C– C–/Com 16 P UC HRZSE 0.01 C+ NG C– C–/Com 17 N UC HRZSE 0.06 C– C– –/Dis 33w 18 N BC HRZSEO 0.06 C+ NG C– –/Dis 41w 19 N BC HRZSEO 0.12 –/Dis 5w –/Dis 5w –/Dis 5w 20 P NC HRZSEKEthC 0.25 C+ NG C– C–/Com C+ at 60w: Eth reverted 21 N BC NG 0.03 C+ NG C– C–/Com 22 N UC NG 0.01 C– –/Dis 18w –/Dis 18w 23 N NC NG NG C– C– C–/Com 24* N NC HRZSEOKEthC 0.03 –/Dis 2w –/Dis 2w –/Dis 2w ↵a BR, background regimen; Com, completed; Dis, discontinued; N, negative; NG or NS, no growth or no sample; P, positive; w, week. Chest radiography: BC, bilateral cavitary disease; CXR, chest radiograph; NC, noncavitary disease (no cavity = ≤2-cm diameter); UC, unilateral cavitary disease. Drugs: C, capreomycin; E, ethambutol; Eth, ethionamide; H, isoniazid; K, kanamycin; O, ofloxacin; R, rifampin; S, streptomycin; Z, pyrazinamide. Drug susceptibility tests were performed using the agar proportion method for the background regimen. TMC207 MIC, MIC obtained with a resazurin microtiter assay.
↵* , Subjects withdrawn at 2 weeks because of XDR TB diagnosed from sputum submitted prior to enrollment;
↵** , subject not included in efficacy population because of negative baseline culture.
