Background: We compared outcomes up to 24 months after treatment initiation for rifampicin-resistant tuberculosis (RR-TB) patients in South Africa treated with a short, all-oral bedaquiline-containing regimen (bedaquiline group), or a short, injectable-containing regimen (injectable group). Methods: RR-TB patients eligible for a short regimen starting treatment between 1 January and 31 December 2017 with a bedaquiline-containing or WHO recommended injectable-containing treatment regimen of 9 to 12 months, registered with their national ID in the drug-resistant TB database and with known age, sex, and HIV status were eligible for study inclusion. To compare regimens, we exactly matched patients on HIV-infection, previous TB treatment history, baseline acid-fast bacilli smear and culture result, and propensity score matched patients on age, sex, and isoniazid susceptibility status, using logistic regression with generalized linear mixed models to estimate adjusted odds ratios (aOR) and 95% confidence intervals (95%CI). Results: Overall, 1,387 of the 10,152 RR-TB patients treated during 2017 met inclusion criteria, of whom 688 received the bedaquiline-containing regimen and 699 patients received the injectable-containing regimen. Four patients (0.6%) had treatment failure and/or recurrence, 44 (6.4%) were lost to follow-up, and 162 (23.5%) died in the bedaquiline group, compared to 17 (2.4%), 87 (12.4%), and 199 (28.5%), respectively, in the injectable group. Patients in the bedaquiline group had 1.8 (95%CI 1.4 to 2.4) times higher odds of treatment success at 24 months and 0.6 (0.4 to 0.8) times lower odds of loss to follow-up. This was consistent in stratified analyses on HIV-status, AFB smear positivity, and previous treatment history. The bedaquiline group had lower odds of mortality during treatment (0.5, 95%CI 0.4 to 0.7), but not post treatment (1.1, 95%CI 0.7 to 1.7). Conclusion: Patients in the bedaquiline group experienced significantly higher rates of treatment success at 24 months compared to the injectable group. The analysis supports the use of short bedaquiline-containing regimens in eligible patients. Funding: WHO Global TB Programme. Declaration of Interest: We declare no competing interests. Ethical Approval: This analysis was approved by Human Research Ethics Committee, Medical of University of Witwatersrand (#M150340, March 2015).
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