A recent landmark clinical trial has provided compelling evidence that drastically shortened antibiotic regimens can safely and effectively prevent active tuberculosis (TB) among exposed individuals. This research, conducted by an international team led by Richard Chaisson of the Johns Hopkins School of Medicine and published in PLOS Medicine, challenges the entrenched World Health Organization (WHO) guidelines that have long recommended prolonged six to nine-month preventive treatment courses. By demonstrating that both a one-month daily regimen and a three-month weekly regimen of isoniazid and rifapentine yield comparably high treatment completion rates and similarly low adverse effect profiles, the study opens the door to more accessible and widely adoptable TB preventive strategies.
Tuberculosis remains a global health scourge, causing significant morbidity and mortality worldwide. Preventive treatment is a cornerstone strategy aimed at halting latent infections from progressing to active disease. However, the traditional preventive therapies’ length — spanning from six to nine months — has posed a formidable barrier to adherence. Non-compliance undermines the treatment’s effectiveness, perpetuating transmission cycles and thwarting public health objectives. Shorter treatment courses, therefore, represent a critical advancement that could revolutionize TB management. Yet, before this study, data comparing the safety and acceptability of ultra-short regimens in populations without HIV was limited.
In the rigorous randomized controlled trial that enrolled 500 participants in Brazil, none of whom were living with HIV, researchers sought to fill this knowledge gap. Participants, exposed to TB in the household or workplace, were randomly assigned to one of two treatment arms: a one-month daily dosing of isoniazid and rifapentine or a three-month regimen with weekly doses of the same antibiotics. The trial design capitalized on randomized allocation to ensure comparability between groups, while comprehensive monitoring captured detailed adherence patterns and adverse events.
Remarkably, the one-month regimen demonstrated an 89.6% treatment completion rate, slightly surpassing the 84.1% completion observed in the three-month weekly group. These rates are among the highest reported for TB preventive therapy, underscoring the tolerability and feasibility of ultra-short courses. Importantly, adverse events in both study arms were predominantly mild or moderate, with no significant differences in frequency or severity. The findings attest to the safety profile of rifapentine combined with isoniazid over such truncated durations.
This trial’s implications for global TB control are profound. Shortened regimens can dramatically reduce the treatment burden on patients, health systems, and communities. By facilitating easier adherence through reduced exposure to medications, side effects, and clinic visits, ultra-short preventive therapy regimens could improve uptake and completion rates substantially. This development is vital in high-burden settings like Brazil, where TB remains endemic and healthcare resources are often stretched thin.
The study authors emphasize that expanding access to preventive therapies remains pivotal for global TB eradication endeavors. The findings provide robust evidence enabling clinicians and policymakers to confidently incorporate one-month daily rifapentine and isoniazid courses into treatment guidelines. The availability of newer generic formulations that patients can take at home further enhances the potential reach of these regimens, reducing barriers related to healthcare access disparities.
Moreover, the study’s rigorous methodology, including its randomized design, large sample size, and location in a TB-endemic setting, lends credibility to its conclusions. Its direct head-to-head comparison of the one-month and three-month regimens fills a critical evidence void previously unaddressed, particularly in people without HIV exposure. This research thereby strengthens the scientific basis for updating international recommendations.
Experts involved in the trial highlight the transformational nature of these ultra-short regimens for TB prevention. By comparing 6-9 month daily therapies with regimens lasting only a month or twelve weekly doses, they have demonstrated a paradigm shift in treatment adherence and safety. This work signals new hope for scaling effective preventive therapies, reducing TB incidence, and ultimately saving millions of lives globally.
The study also sheds light on patient-centered factors crucial for treatment success. Shorter, well-tolerated treatment options can minimize the logistical and psychological burdens associated with lengthy therapies, fostering sustained engagement and completion. This is especially critical in high-transmission urban and occupational settings where TB exposure risk is elevated.
Beyond Brazil, the trial’s findings are relevant to other high-burden countries seeking evidence-based strategies to accelerate TB decline. By providing data demonstrating equivalence between the one- and three-month regimens, the study empowers national programs to tailor preventive treatment approaches based on local infrastructure, patient preferences, and resource availability.
Nevertheless, the authors recognize that preventive therapy alone cannot eliminate TB without parallel investments in diagnostics, case finding, and social determinants of health. Yet, this advancement in regimen shortening represents a vital piece of the complex puzzle of TB control, offering a practical lever for enhancing preventive intervention effectiveness.
In summary, this pivotal clinical trial conclusively demonstrates that ultra-short regimens of rifapentine and isoniazid administered over one or three months are both safe and effective for preventing active TB in exposed populations. These findings disrupt traditional long-course paradigms, offering a path to improved treatment completion and expanded preventive coverage worldwide. Incorporating these regimens into public health strategies promises to accelerate progress toward global TB elimination goals, transforming the landscape of TB prevention and patient care.
Subject of Research: People exposed to tuberculosis (TB) in household or workplace settings
Article Title: Acceptability and safety of one versus three months of rifapentine and isoniazid to prevent tuberculosis in people exposed in the household or workplace in Brazil: The Ultra-Curto randomized controlled trial
News Publication Date: February 10, 2026
Web References:
- PLOS Medicine article DOI: 10.1371/journal.pmed.1004758
- National Institute of Allergy and Infectious Diseases: https://www.niaid.nih.gov/
References:
Durovni B, Cordeiro-Santos M, Cavalcante SC, Spener-Gomes R, Garcia J, Cohn S, et al. (2026) Acceptability and safety of one versus three months of rifapentine and isoniazid to prevent tuberculosis in people exposed in the household or workplace in Brazil: The Ultra-Curto randomized controlled trial. PLoS Med 23(2): e1004758.
Image Credits: Beatriz Kohler (CC-BY 4.0)
Keywords: tuberculosis prevention, rifapentine, isoniazid, preventive therapy, TB treatment adherence, clinical trial, Brazil, high-burden countries, short-course regimen, latent tuberculosis infection
