Nine-month all-oral regimen for MDR/RR-TB in Lesotho: safety and effectiveness by HIV

Background: Individuals living with HIV have been under-represented in operational research and trials of all-oral regimens for multidrug- and rifampicin-resistant tuberculosis (MDR/RR-TB) treatment. We report outcomes from a prospective observational cohort study of a nine-month regimen comprised of bedaquiline, linezolid, a fluoroquinolone, delamanid, and clofazimine, in Lesotho, a setting with a high prevalence of HIV infection. Methods: We analyzed patients who initiated the regimen between 2020 and 2023. Overall, and by HIV status, we characterized treatment safety by summarizing the frequency and timing of clinically relevant adverse events. We described treatment effectiveness at the end of treatment and sustained treatment success eighteen months after treatment initiation. Results: Two hundred and fifty-five patients who initiated the shortened all-oral regimen were included in the analysis, of whom 161 (63.1%) were living with HIV. Regardless of HIV status, the most frequent clinically relevant adverse event was peripheral neuropathy, followed by myelosuppression. The estimated unadjusted rates of sustained treatment success at 18 months post-treatment initiation were 86.4% (95% confidence interval (CI): 81.4%, 90.5%) overall, 85.0% (95% CI: 78.2%, 90.4%) among patients living with HIV, and 88.8% (95% CI: 80.3%, 94.5%) among people without HIV. Conclusions: The effectiveness of the nine-month all-oral regimen was excellent. Although adverse events were common, they were manageable and did not appear to substantially impact treatment success. Results were similar regardless of HIV status, supporting the use of this regimen in this population.