Global Health
Initiation of bedaquiline-containing regimens and risk of treatment failure among persons on treatment for multidrug resistant-tuberculosis Sarah Brumfield* Sarah Brumfield Pawandeep Kaur Afranio Kritski Valeria Rolla Sanjay Gaikwad Sonali Sarkar Tester Ashavaid Padmapriyadarsini Chandrasekaran Amrose Pradeep Timothy Sterling C Robert Horsburgh
Multidrug resistant-tuberculosis (MDR-TB), which is resistant to the two most effective first-line TB medications, is a threat to global TB control. Historically, MDR-TB treatment has been characterized by long duration and substantial toxicity. In recent years, shorter and more tolerable regimens have been developed; bedaquiline is a cornerstone of these newer regimens. We examined whether bedaquiline initiation at the start of treatment was associated with improved treatment outcomes among those with MDR-TB.
Participants were enrolled at TB treatment sites in India and Brazil from January 2019 through December 2022. Treatment regimens were selected by local clinical providers. Baseline visits occurred within 14 days of treatment initiation, and participants were followed through one year after treatment completion. We compared regimens in which bedaquiline was initiated within 28 days of the baseline visit to those that did not initiate bedaquiline within 28 days, regardless of whether bedaquiline was initiated later. Sputum smear and culture were performed at week 16 and subsequently. Treatment failure was defined as a positive culture at the last on-treatment visit or after treatment completion, TB recurred after treatment completion, death occurred before the end of treatment, or a treatment failure was reported by study staff. We performed a Cox proportional hazards analysis adjusted for country of residence, age, HIV status, presence of lung cavitation at baseline, and self-reported treatment adherence.
A total of 312 participants completed 26,780 weeks of follow-up, during which 57 (18%) participants experienced treatment failure. The adjusted hazard ratio for treatment failure comparing bedaquiline at initiation to non-bedaquiline baseline regimens was 0.59 (0.30, 1.16).
Our findings suggest that initiating bedaquiline at baseline was associated with a modest but not significant improvement in treatment outcomes in this population.