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Completion Rate and Safety of Tuberculosis Infection Treatment With Shorter Regimens

We have found that shorter regimens for TB infection (3HP or 4R) are safe and have higher completion rates than 9H. BACKGROUND: The traditional treatment of tuberculosis (TB) infection (9 months of daily isoniazid [9H]) is safe but completion rates of <50% are reported. Shorter regimens (3 months of once-weekly isoniazid and rifapentine [3HP] or 4 months of daily rifampin [4R]) are associated with improved adherence in adults. METHODS: This was a retrospective cohort study (2014–2017) of children (0–18 years old) seen at a children’s TB clinic in a low-incidence nation. We compared the frequency of completion and adverse events (AEs) in children receiving 3HP, 4R, and 9H; the latter 2 regimens could be administered by families (termed self-administered therapy [SAT]) or as directly observed preventive therapy (DOPT); 3HP was always administered under DOPT. RESULTS: TB infection treatment was started in 667 children: 283 (42.4%) 3HP, 252 (37.8%) 9H, and 132 (19.8%) 4R. Only 52% of children receiving 9H via SAT completed therapy. Children receiving 3HP were more likely to complete therapy than the 9H (SAT) group (odds ratio [OR] 27.4, 95% confidence interval [CI]: 11.8–63.7). Multivariate analyses found receipt of medication under DOPT (OR: 5.72, 95% CI: 3.47–9.43), increasing age (OR: 1.09, 95% CI: 1.02–1.17), and the absence of any AE (OR: 1.70, 95% CI: 0.26–0.60) to be associated with completing therapy. AEs were more common in the 9H group (OR: 2.51, 95% CI: 1.48–4.32). Two (0.9%) children receiving 9H developed hepatotoxicity; no child receiving 3HP or 4R developed hepatotoxicity. CONCLUSIONS: Shorter regimens are associated with increased completion rates and fewer AEs than 9H.