Palwasha Y Khan1,2,3, Molly F Franke4,5,3, Catherine Hewison6, Kwonjune J Seung4,7, Helena Huerga8, Sidney Atwood7, Saman Ahmed9, Munira Khan10, Tanha Sultana11, Mohammad Manzur-Ul-Alam11, Luan N Q Vo12,13, Leonid Lecca14, Kalkidan Yae15, Serik Kozhabekov16, Meseret Tamirat17, Alain Gelin18, Stalz C Vilbrun19, Marina Kikvidze20, Jamil Faqirzai21, Abdullaat Kadyrov22, Alena Skrahina23, Anita Mesic24, Nana Avagyan6, Mathieu Bastard8, Michael L Rich4,7, Uzma Khan12,3, Carole D Mitnick4,5,3. 1. Interactive Research and Development Global, Singapore palwasha.khan@lshtm.ac.uk. 2. Clinical Research Dept, Faculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, London, UK. 3. These authors contributed equally. 4. Partners In Health, Boston, MA, USA. 5. Dept of Global Health and Social Medicine, Harvard Medical School, Boston, MA, USA. 6. Medical Dept, Médecins Sans Frontières, Paris, France. 7. Division of Global Health Equity, Brigham and Women's Hospital, Boston, MA, USA. 8. Field Epidemiology Dept, Epicentre, Paris, France. 9. Interactive Research and Development, Karachi, Pakistan. 10. Interactive Research and Development, Durban, South Africa. 11. Interactive Research and Development, Dhaka, Bangladesh. 12. Interactive Research and Development Global, Singapore. 13. Friends for International TB Relief, Ho Chi Minh City, Vietnam. 14. Socios En Salud Sucursal Peru, Lima, Peru. 15. Partners In Health, Ethiopia, Addis Ababa, Ethiopia. 16. Partners In Health, Almaty, Kazakhstan. 17. Partners In Health, Lesotho, Maseru, Lesotho. 18. Zanmi Lasante, Port-au-Prince, Haiti. 19. Haitian Group for the Study of Kaposi's Sarcoma and Opportunistic Infections (GHESKIO), Port-au-Prince, Haiti. 20. Médecins Sans Frontières, Georgia. 21. Médecins Sans Frontières, Armenia. 22. Médecins Sans Frontières, Kyrgyzstan. 23. Médecins Sans Frontières, Belarus. 24. Médecins Sans Frontières, Amsterdam, The Netherlands.
Abstract
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.
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.