All-oral longer regimens are effective for the management of multidrug-resistant tuberculosis in high-burden settings.

Background: Recent World Health Organization guidance on drug-resistant tuberculosis treatment de-prioritised injectable agents, in use for decades, and endorsed all-oral longer regimens. However, questions remain about the role of the injectable agent, particularly in the context of regimens using new and repurposed drugs. We compared the effectiveness of an injectable-containing regimen to that of an all-oral regimen among patients with drug-resistant tuberculosis who received bedaquiline and/or delamanid as part of their multidrug regimen.
Methods: Patients with a positive baseline culture were included. 6-month culture conversion was defined as two consecutive negative cultures collected >15 days apart. We derived predicted probabilities of culture conversion and relative risk using marginal standardisation methods.
Results: Culture conversion was observed in 83.8% (526 out of 628) of patients receiving an all-oral regimen and 85.5% (425 out of 497) of those receiving an injectable-containing regimen. The adjusted relative risk comparing injectable-containing regimens to all-oral regimens was 0.96 (95% CI 0.88-1.04). We found very weak evidence of effect modification by HIV status: among patients living with HIV, there was a small increase in the frequency of conversion among those receiving an injectable-containing regimen, relative to an all-oral regimen, which was not apparent in HIV-negative patients.
Conclusions: Among individuals receiving bedaquiline and/or delamanid as part of a multidrug regimen for drug-resistant tuberculosis, there was no significant difference between those who received an injectable and those who did not regarding culture conversion within 6 months. The potential contribution of injectable agents in the treatment of drug-resistant tuberculosis among those who were HIV positive requires further study.
Competing Interests: Conflict of interest: P.Y. Khan reports grants from Unitaid, during the conduct of the study; other (study drug donations coordinated by the endTB Consortium) from Otsuka Pharamceutical and Janssen, outside the submitted work. Conflict of interest: M.F. Franke reports grants from Unitaid, during the conduct of the study. Conflict of interest: C. Hewison reports grants from Unitaid, during the conduct of the study. Conflict of interest: K.J. Seung reports grants from Unitaid, during the conduct of the study. Conflict of interest: H. Huerga reports grants from Unitaid, during the conduct of the study. Conflict of interest: S. Atwood has nothing to disclose. Conflict of interest: S. Ahmed reports grants from Unitaid, during the conduct of the study; other (study drug donations coordinated by the endTB Consortium) from Otsuka Pharamceutical and Janssen Pharmaceutical, outside the submitted work. Conflict of interest: M. Khan has nothing to disclose. Conflict of interest: T. Sultana has nothing to disclose. Conflict of interest: M. Manzur-ul-Alam has nothing to disclose. Conflict of interest: L.N.Q. Vo reports grants and non-financial support (drugs/equipment) from Unitaid via IRD Global during the conduct of the study. Conflict of interest: L. Lecca has nothing to disclose. Conflict of interest: K. Yae has nothing to disclose. Conflict of interest: S. Kozhabekov has nothing to disclose. Conflict of interest: M. Tamirat has nothing to disclose. Conflict of interest: A. Gelin has nothing to disclose. Conflict of interest: S.C. Vilbrun has nothing to disclose. Conflict of interest: M. Kikvidze has nothing to disclose. Conflict of interest: J. Faqirzai has nothing to disclose. Conflict of interest: A. Kadyrov has nothing to disclose. Conflict of interest: A. Skrahina has nothing to disclose. Conflict of interest: A. Mesic has nothing to disclose. Conflict of interest: N. Avagyan has nothing to disclose. Conflict of interest: M. Bastard reports grants from Unitaid, during the conduct of the study. Conflict of interest: M.L. Rich reports grants from Unitaid, during the conduct of the study; personal fees for consultancy from World Health Organization, other (study drug donations coordinated by the endTB Consortium) from Otsuka Pharamceutical and Janssen, outside the submitted work. Conflict of interest: U. Khan reports grants from Unitaid, during the conduct of the study; other (study drug donations coordinated by the endTB Consortium) from Otsuka Pharamceutical and Janssen, outside the submitted work. Conflict of interest: C.D. Mitnick reports a grant from Unitaid to fund the study and that the endTB Consortium coordinated donations of delamanid (Otsuka Pharmaceutical) and bedaquiline (Janssen) to be used for treatment by some of the patients included in the endTB Observational Study.
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