Estimating Post-treatment Recurrence After Multidrug-Resistant Tuberculosis Treatment Among Patients With and Without Human Immunodeficiency Virus: The Impact of Assumptions About Death and Missing Follow-up

Sauer S.M. Mitnick C.D. Khan U. Hewison C. Bastard M. Holtzman D. Law S. Khan M. Padayachee S. Ahmed S. Isani A.K. Krisnanda A. Vilbrun S.C. Bektasov S. Kumsa A. Docteur W. Tintaya K. McNicol M. Atshemyan H. Voynilo T. Thwe T.T. Seung K. Rich M. Huerga H. Khan P. Franke M.
15 January 2024 Oxford University Press

Clinical Infectious Diseases
2024 #78 Issue 1 164 - 171 pp.

Background. Quantification of recurrence risk following successful treatment is crucial to evaluating regimens for multidrug- or rifampicin-resistant (MDR/RR) tuberculosis (TB). However, such analyses are complicated when some patients die or become lost during post-treatment follow-up. Methods. We analyzed data on 1991 patients who successfully completed a longer MDR/RR-TB regimen containing bedaquiline and/or delamanid between 2015 and 2018 in 16 countries. Using 5 approaches for handling post-treatment deaths, we estimated 6-month post-treatment TB recurrence risk overall and by HIV status. We used inverse-probability weighting to account for patients with missing follow-up and investigated the impact of potential bias from excluding these patients without applying inverse-probability weights. Results. The estimated TB recurrence risk was 7.4/1000 (95% credible interval: 3.3–12.8) when deaths were handled as non-recurrences and 7.6/1000 (3.3–13.0) when deaths were censored and inverse-probability weights were applied to account for the excluded deaths. The estimated risks of composite recurrence outcomes were 25.5 (15.3–38.1), 11.7 (6.4–18.2), and 8.6 (4.1–14.4) per 1000 for recurrence or (1) any death, (2) death with unknown or TB-related cause, or (3) TB-related death, respectively. Corresponding relative risks for HIV status varied in direction and magnitude. Exclusion of patients with missing follow-up without inverse-probability weighting had a small impact on estimates. Conclusions. The estimated 6-month TB recurrence risk was low, and the association with HIV status was inconclusive due to few recurrence events. Estimation of post-treatment recurrence will be enhanced by explicit assumptions about deaths and appropriate adjustment for missing follow-up data.

competing events , inverse-probability weighting , MDR-TB , missing follow-up , post-treatment recurrence

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Department of Global Health and Social Medicine, Harvard Medical School, Boston, MA, United States
Interactive Research and Development (IRD) Global, Singapore, Singapore
Médecins Sans Frontières, Paris, France
Epicentre, Paris, France
Partners in Health, Lesotho, Maseru, Lesotho
IRD Global, Durban, South Africa
IRD Global, Karachi, Pakistan
Centers for Disease Control and Prevention, Directorate General Health Services, Sindh, Pakistan
IRD Global, Jakarta, Indonesia
The Haitian Group for the Study of Kaposi’s Sarcoma and Opportunistic Infections (GHESKIO), Port-au-Prince, Haiti
TB National TB Center, Kazakhstan
Ministry of Health, Addis Ababa, Ethiopia
Zanmi Lasante, Cange, Haiti
Socios en Salud, Lima, Peru
Médecins Sans Frontières, Tbilisi, Georgia
Médecins Sans Frontières, Yerevan, Armenia
Médecins Sans Frontières, Minsk, Belarus
Médecins Sans Frontières, Yangon, Myanmar
Partners in Health, Boston, MA, United States
Brigham and Women’s Hospital, Boston, MA, United States
Department of Clinical Research, London School of Hygiene & Tropical Medicine, London, United Kingdom
Department of Global Health and Social Medicine, Harvard Medical School, 641 Huntington Avenue, Boston, 02115, MA, United States

Department of Global Health and Social Medicine
Interactive Research and Development (IRD) Global
Médecins Sans Frontières
Epicentre
Partners in Health
IRD Global
IRD Global
Centers for Disease Control and Prevention
IRD Global
The Haitian Group for the Study of Kaposi’s Sarcoma and Opportunistic Infections (GHESKIO)
TB National TB Center
Ministry of Health
Zanmi Lasante
Socios en Salud
Médecins Sans Frontières
Médecins Sans Frontières
Médecins Sans Frontières
Médecins Sans Frontières
Partners in Health
Brigham and Women’s Hospital
Department of Clinical Research
Department of Global Health and Social Medicine

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