Safety and Effectiveness of 3 Novel All-Oral Shortened Regimens for Rifampicin- or Multidrug-Resistant Tuberculosis in Kazakhstan

Author:

Rashitov Makhmujan1,Franke Molly F23ORCID,Trevisi Letizia2,Bekbolatova Gulzhanat4,Shalimova Julia5,Eshmetov Gafurzhan6,Bektasov Sagit7,LaHood Allison23,Arlyapova Nataliya8,Osso Elna2,Yedilbayev Askar9,Korotych Oleksandr9,Ciobanu Anisoara9,Skrahina Alena10,Mitnick Carole D2811,Seung Kwonjune J811,Algozhin Yerkebulan1,Rich Michael L811

Affiliation:

1. Partners In Health Kazakhstan , Almaty , Kazakhstan

2. Department of Global Health and Social Medicine, Harvard Medical School , Boston, Massachusetts , USA

3. Department of Epidemiology, Harvard T.H. Chan School of Public Health , Boston, Massachusetts , USA

4. Atyrau Regional Center of Phthisiopulmonology , Atreyu , Kazakhstan

5. Karaganda Regional Center of Phthisiopulmonology , Karaganda , Kazakhstan

6. Turkistan Regional Center of Phthisiopulmonology , Turkistan , Kazakhstan

7. National Scientific Center of Phthisiopulmonology , Almaty , Kazakhstan

8. Partners In Health , Boston, Massachusetts , USA

9. World Health Organization, Regional Office for Europe , Copenhagen , Denmark

10. The Republican Scientific and Practical Centre for Pulmonology and Tuberculosis , Minsk , Belarus

11. Division of Global Health Equity, Brigham and Women's Hospital , Boston, Massachusetts , USA

Abstract

Abstract Background In 2019, the World Health Organization called for operational research on all-oral shortened regimens for multidrug- and rifampicin-resistant tuberculosis (MDR/RR-TB). We report safety and effectiveness of three 9-month all-oral regimens containing bedaquiline (Bdq), linezolid (Lzd), and levofloxacin (Lfx) and reinforced with cycloserine (Cs) and clofazimine (Cfz), delamanid (Dlm) and pyrazinamide (Z), or Dlm and Cfz. Methods We conducted a prospective cohort study of patients initiating treatment for pulmonary MDR/RR-TB under operational research conditions at public health facilities in Kazakhstan. Participants were screened monthly for adverse events. Participants with baseline resistance were excluded from the study and treated with a longer regimen. We analyzed clinically relevant adverse events of special interest in all participants and sputum culture conversion and end-of-treatment outcomes among individuals who were not excluded. Results Of 510 participants, 41% were women, the median age was 37 years (25th–75th percentile: 28–49), 18% had a body mass index <18.5 kg/m2, and 51% had cavitary disease. A total of 399 (78%) initiated Bdq-Lzd-Lfx-Cs-Cfz, 83 (16%) started Bdq-Lzd-Lfx-Dlm-Z, and 28 (5%) initiated Bdq-Lzd-Lfx-Dlm-Cfz. Fifty-eight individuals (11%) were excluded from the study, most commonly due to identification of baseline drug resistance (n = 52; 90%). Among the remaining 452 participants, treatment success frequencies were 92% (95% CI: 89–95%), 89% (95% CI: 80–94%), and 100% (95% CI: 86–100%) for regimens with Cs/Cfz, Dlm/Z, and Dlm/Cfz, respectively. Clinically relevant adverse events of special interest were uncommon. Conclusions All regimens demonstrated excellent safety and effectiveness, expanding the potential treatment options for patients, providers, and programs.

Funder

Global Fund to Fight AIDS, Tuberculosis, and Malaria

National Institute of Allergy and Infectious Diseases

Publisher

Oxford University Press (OUP)

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