Longer vs. shorter all-oral bedaquiline-based regimens for drug-resistant tuberculosis: real-world evidence from a high-burden setting.

BACKGROUND

The World Health Organization recommends all-oral bedaquiline-based regimens for drug-resistant tuberculosis (DR-TB), including a longer M/XDR-TB regimen (18-20 months) and a shorter RR/MDR-TB regimen (9-11 months). Comparative effectiveness data under routine programmatic conditions remain limited.

OBJECTIVE

To compare clinical and microbiological outcomes of longer versus shorter all-oral treatment regimens.

METHODS

We conducted a prospective observational cohort study between January and December 2022. Patients with pulmonary or extrapulmonary RR/MDR-TB were enrolled and treated according to national programmatic guidelines. Six-month culture conversion and end-of-treatment clinical outcomes were compared between longer and shorter all-oral bedaquiline-based regimens using multivariable logistic regression adjusted for pre-specified confounders.

RESULTS

Of 1427 patients screened, 894 (62.6%) were included; 691 (77.3%) received the longer regimen and 203 (22.7%) the shorter regimen. Baseline demographic and clinical characteristics were broadly comparable, although resistance profiles differed because regimen allocation was guided by drug susceptibility testing and programmatic eligibility criteria. Six-month culture results were available for 778 (87.0%) patients; 96 (10.7%) died and 20 (2.3%) were lost to follow-up. Culture conversion was significantly higher with the longer regimen than the shorter regimen (579/596, 97.1% vs. 146/182, 80.2%; p < 0.001). In intention-to-treat analysis, favorable outcomes occurred in 525/691 (76.0%) patients receiving the longer regimen and 135/203 (66.5%) receiving the shorter regimen (p = 0.006). The longer regimen was independently associated with favorable outcomes (adjusted odds ratio 1.58, 95% CI 1.15-2.17; p = 0.004).

CONCLUSIONS

Baseline demographic and clinical characteristics were broadly comparable, although resistance profiles differed because regimen allocation was guided by drug susceptibility testing and programmatic eligibility criteria.