Acceptance, completion, and safety of the 3HR regimen for latent tuberculosis infection: a prospective cohort study in China.

BACKGROUND

Tuberculosis preventive treatment (TPT) is essential for reducing the progression of latent tuberculosis infection (LTBI) to active disease, yet real-world implementation often faces substantial attrition. This study evaluated the acceptance, completion, and safety of the 3-month daily isoniazid plus rifampicin regimen (3HR) among close contacts in a high-burden setting in China.

METHODS

We conducted a prospective observational cohort study among tuberculin skin test-positive close contacts from January 2024 to June 2025. Participants voluntarily chose to initiate or decline 3HR. Acceptance, completion, and adverse events (AEs) were prospectively recorded. Multivariable logistic regression models were used to identify predictors of uptake and completion, and a sensitivity analysis assessed the differential impact of hepatic versus non-hepatic AEs.

RESULTS

Among 617 eligible contacts, 520 (84.3%) accepted TPT. Acceptance was significantly higher among school than household contacts (96.0% vs. 76.1%; p < 0.001), and school contact status was the strongest predictor of uptake (adjusted odds ratio [aOR] 14.20; 95% CI 5.48-36.82). Among the 520 initiators, 382 (73.5%) completed treatment. Demographic factors were not associated with completion, whereas AEs markedly reduced completion (aOR 0.25; 95% CI 0.14-0.44). A total of 56 participants (10.8%) experienced at least one AE; hepatic events were the most frequent (73.2%) and accounted for most discontinuations. Subjective intolerance far exceeded clinically confirmed AEs (75 vs. 20). Sensitivity analyses confirmed that both hepatic and non-hepatic AEs independently reduced completion.

CONCLUSION

In this real-world implementation evaluation, the 3HR regimen demonstrated high programmatic acceptance, particularly in school settings; however, treatment completion was constrained by both perceived and clinically verified AEs. These findings suggest that optimizing TPT delivery requires strengthened safety monitoring, structured symptom counseling, and targeted mobilization strategies to improve uptake, particularly among household contacts.