Safety and Effectiveness of an All-Oral, Bedaquiline-Based, Shorter Treatment Regimen for Rifampicin-Resistant Tuberculosis in High Human Immunodeficiency Virus (HIV) Burden Rural South Africa: A Retrospective Cohort Analysis

• Published in: Clinical infectious diseases 2021-11, Vol.73 (9), p.e3563-e3571
• Main Authors: Tack, Ilse, Dumicho, Asnake, Ohler, Liesbet, Shigayeva, Altynay, Bulti, Abera Balcha, White, Kenneth, Mbatha, Mduduzi, Furin, Jennifer, Isaakidis, Petros
• Format: Article
• Language: English
• Subjects: Online only
• ISSN: 1058-4838; 1537-6591
• DOI: 10.1093/cid/ciaa1894

Abstract Background At the end of 2018, South Africa updated its all-oral regimen, to include bedaquiline (BDQ) and 2 months of linezolid (LZD) for all patients initiating the shorter 9–12 months regimen for rifampicin-resistant tuberculosis (RR-TB). We assessed a group of patients in rural KwaZulu-Natal for safety and effectiveness of this treatment regimen under programmatic conditions. Methods We conducted a retrospective cohort analysis on RR-TB patients treated with a standardized all-oral short regimen between 1 July 2018 and 30 April 2019 in 3 facilities in King Cetshwayo District. An electronic register (EDR web) and facility-based clinical charts were used to collect variables, which were entered into an Epi-Info database. Results Our cohort included 117 patients; 68.4% (95% confidence interval [CI]: 59.3–76.3) tested positive for human immunodeficiency virus (HIV). The median time to culture conversion was 56 days (95% CI: 50–57). Treatment success was achieved in 75.2% (95% CI: 66.5–82.3) of patients. Mortality within the cohort was 12.8% (95% CI: 7.8–20.3). Anemia was the most frequent severe adverse event (AE). The median time to develop severe anemia was 7.1 weeks (interquartile range [IQR] 4.0–12.9) after treatment initiation. LZD was interrupted in 25.2% (95% CI: 17.8–34.5) of participants. Conclusions An all-oral shorter regimen, including BDQ and LZD as core drugs for the treatment of RR-TB, shows good outcomes, in a high HIV burden rural setting. AEs are common, especially for LZD, but could be managed in the program setting. Support is needed when introducing new regimens to train staff in the monitoring, management, and reporting of AEs. An all-oral regimen, combining linezolid and bedaquiline, for the treatment of rifampicin-resistant tuberculosis shows good outcomes, irrespective of human immunodeficiency virus (HIV) status or CD4 level. Linezolid accounted for nearly half of severe adverse events and warrants close monitoring for myelosuppression and neuropathy.