Programmatic impact and cost-effectiveness of scaling up the short-course 3HP regimen for tuberculosis preventive treatment in Brazil

Background Tuberculosis preventive therapy (TPT) is critical in interrupting progression to disease, transmission and reducing incidence rates. Nonetheless, high costs have been barriers towards the expansion of shorter patient-friendly drug regimens. In 2019, a Unitaid-led deal reduced rifapentine costs by over 70%, facilitating Brazil’s implementation of 3 months of rifapentine+isoniazid (3HP), a short-course TPT regimen, in its public health system. We evaluated the health and economic impact of Brazil’s implementation of this patient-friendly regimen for short-course TPT. Methods We analysed surveillance data on 171 174 individuals initiating TPT from January 2019 to December 2024. A mixed-effects spatiotemporal Bayesian model estimated quarterly TPT initiation trends under (1) observed 3HP rollout versus a no-3HP counterfactual (Q3 2021–Q4 2024) and (2) projected universal 3HP coverage (Q1 2025–Q4 2027) versus extended no-3HP adoption. Cost-effectiveness analysis quantified active tuberculosis (TB) cases and disability-adjusted life-years (DALYs) averted, alongside costs, incremental cost-effectiveness ratios, net monetary benefits (NMBs) and return on investment of TPT under each 3HP coverage scenario. Results From 2022 to 2024, 3HP scale-up produced 37 508. 4 (95% credible intervals (CrIs) 31 405. 2 to 43 631. 6) additional TPT initiations, averted an estimated 15 002 DALYs (95% CrI 8985. 6 to 21 031. 15) and yielded NMBs of US122. 7 million (95% CrI US63. 8 to US198. 2 million). Under a proposed universal coverage (2025–2027), projected gains included 72 080. 1 (95% CrI 62 323. 7 to 81 836. 4) additional individuals starting TPT, with subsequent 26 139 DALYs averted (95% CrI 14 117 to 38 762) and NMBs of US214. 5 million (95% CrI US103. 0 to US362. 8 million), indicating strong economic dominance over no-3HP adoption. Finally, TPT with 3HP’s implementation was estimated to return US1. 31 (95% CrI US0. 97 to US1. 62) to the health system for every US1 invested. Conclusions In Brazil, large-scale implementation of a patient-friendly short-course regimen (3HP) was effective and likely cost-saving for a resource-strained public health system. Our evaluation provides robust, real-world evidence that implementing this regimen improved TPT coverage and completion nationwide while reducing costs and TB disease burden.