Bedaquiline containing regimens for the treatment of multi- and extensively drug-resistant tuberculosis at the programmatic level in Belarus. Prospective cohort study

<b>Background:</b> Bedaquiline (Bdq), a new drug effective against multi- and extensively drug-resistant tuberculosis (M/XDR-TB), was granted accelerated approval by the United States Food and Drug Administration in 2012. To improve treatment outcomes in patients with M/XDR-TB Bdq has been programmatically introduced in Belarus since July 2015. <b>Methods:</b> Belarus national TB program developed measures to monitor safety and effectiveness Bdq containing regimens prospectively in the countrywide cohort study. <b>Results:</b> By January 1, 2019, cumulative number of M/XDR-TB patients treated with Bdq was 763. Among 275 of them who had final treatment outcomes, 74% were males; 57% previously treated; 53% XDR-TB; 32% pre-XDR-TB (11% FQ, 21% second line injectables resistant). All patients experienced adverse events (AEs). The most common adverse events were: hyperuricemia, hypokalemia, hypomagnesemia, cardiac abnormalities (incl. QT prolongation), myelosuppression (anemia, low platelet count), liver and renal function impairment. Most of the AEs were mild and moderate and did not cause BDQ regimen discontinuation. The following final treatment outcomes were recorded: treatment success - 231 (84%); treatment failure - 8 (3%); lost to follow up - 20 (7%); death - 16 (6%). <b>Conclusions:</b> The results of Belarus countrywide prospective cohort study of Bdq containing regimens used to treat M/XDR-TB showed satisfactory safety profile and good final treatment outcomes even in the cohort with a significant proportion of MDR-TB with advanced drug resistance profile (85% - XDR-TB and pre-XDR-TB).