Author:
Sauer Sara M.,Mitnick Carole D.,Khan Uzma,Hewison Catherine,Bastard Mathieu,Holtzman David,Law Stephanie,Khan Munira,Padayachee Shrivani,Ahmed Saman,Isani Afshan K.,Krisnanda Aga,Vilbrun Stalz Charles,Bektasov Sagit,Kumsa Andargachew,Docteur Wisney,Tintaya Karen,McNicol Mark,Atshemyan Hakob,Voynilo Tatiana,Thwe Thin Thin,Seung Kwonjune,Rich Michael,Huerga Helena,Khan Palwasha,Franke Molly
Abstract
ABSTRACTBackgroundQuantification 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.MethodsWe analyzed data on 1,991 patients who successfully completed a longer MDR/RR-TB regimen containing bedaquiline and/or delamanid between 2015 and 2018 in 16 countries. Using five approaches for handling post-treatment deaths, we estimated the six-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.ResultsThe estimated TB recurrence risk was 6.6 per 1000 (95% confidence interval (CI):3.2,11.2) when deaths were handled as non-recurrences, and 6.7 per 1000 (95% CI:2.8,12.2) when deaths were censored and inverse-probability weights were applied to account for the excluded deaths. The estimated risk of composite recurrence outcomes were 24.2 (95% CI:14.1,37.0), 10.5 (95% CI:5.6,16.6), and 7.8 (95% CI:3.9,13.2) per 1000 for recurrence or 1) any death, 2) death with unknown or TB-related cause, 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 but apparent impact on estimates.ConclusionThe estimated six-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.
Publisher
Cold Spring Harbor Laboratory