Weekly 3HP beats daily rifampicin for tuberculosis infection completion

Tuberculosis infection (TBI), often called latent tuberculosis, is a major target for prevention efforts under the WHO End TB Strategy because treating people who carry the bacteria can stop future cases of active disease. Two short-course treatments that are widely recommended are weekly isoniazid plus rifapentine for 12 weeks (3HP) and daily rifampicin for 16 weeks (4RIF). Until now, those two regimens had not been directly compared in a randomised trial. Corresponding author Greg J. Fox and colleagues set out to compare how well people complete these two regimens in routine clinic settings. They ran a multicentre, open-label, parallel-group, randomised controlled trial at seven tuberculosis clinics in Sydney, Australia, between July 1, 2019, and June 30, 2024. People of any age with TBI were randomised 1:1 by a computer-generated, site-stratified sequence to receive either 3HP or 4RIF. All doses were self-administered. Participants allocated to 3HP received weekly SMS reminders; both groups had standard clinic follow-up. The research focused on whether patients finished their prescribed courses, an important practical measure for real-world tuberculosis prevention programs.

The trial compared two clearly defined regimens. The 3HP arm received isoniazid 15 mg/kg (max 900 mg) plus rifapentine 900 mg once weekly for 12 weeks. The 4RIF arm received rifampicin 10 mg/kg (max 600 mg) daily for 16 weeks. The primary outcome was treatment completion, defined as ingestion of ≥90% of prescribed doses, assessed at the end of treatment. Analyses followed the intention-to-treat principle and included all randomised participants. The study enrolled 210 people: 106 assigned to 3HP and 104 assigned to 4RIF; 121 participants were female and 89 were male. Treatment completion was higher in the 3HP group, with 90 of 106 (84.9%) completing, compared with 68 of 104 (65.4%) in the 4RIF group. The relative risk was 1.30 (95% CI 1.10–1.53) with p=0.002, showing a statistically significant difference. Adverse events of any grade occurred in 26 of 106 (24.5%) in the 3HP group and 21 of 104 (20.2%) in the 4RIF group. No treatment-related deaths were reported. The trial is registered with the Australian New Zealand Clinical Trials Registry (ACTRN12618001672246) and is closed to new enrolments.

These results show that the 3HP regimen, when supported by weekly SMS reminders and standard clinic follow-up, led to substantially higher rates of treatment completion than 4RIF in this trial population. Because completion is a practical measure related to the real-world effectiveness of preventive therapy, higher completion with 3HP suggests it could improve the impact of TBI programs by getting more people through a full preventive course. Safety findings were broadly similar between arms in terms of adverse events, and there were no treatment-related deaths, which supports the acceptability of both options in clinic settings. The authors conclude that their findings support broader implementation of 3HP in TBI programs to improve adherence and outcomes. The study was funded by an Investigator Grant (#2007920) from the Australian National Health and Medical Research Council (NHMRC), with additional in-kind support from Sanofi Pharmaceuticals and assistance from participating clinic staff.