A71-06 Safety and Treatment Completion of 1 Versus 3 Months of Isoniazid and Rifapentine (HP) in Household Contacts of People With Tuberculosis: The One-to-Three Trial

Rationale

Short-course tuberculosis (TB) preventive treatment (TPT) using rifapentine and isoniazid either weekly for 12 weeks (3HP) or daily for one month (1HP) is effective in people with HIV (PWH), but comparative safety and treatment completion data in HIV-negative people are limited. We compared safety and treatment completion of self-administered 1HP and 3HP among HIV-negative household contacts (HHCs) of TB patients.

Methods

“One-to-Three” was a multi-country, randomized, open-label, phase IV trial that enrolled HHCs of rifampicin-susceptible pulmonary TB patients without active TB disease. Participants were randomized by household cluster 1:1 to 1HP or 3HP. Treatment completion was measured by self-report, pill count, and openings of electronic medication devices (EMD) on scheduled medication days. The primary outcomes were completion of ≥ 90% of doses using a composite of the three treatment completion measures and safety, including treatment limiting adverse effects (AEs), ≥Grade 2 targeted AEs, and ≥Grade 3 related AEs. Enrolment began in July 2023 and follow up ended in July 2025.

Results

481 HHCs were enrolled in Indonesia, Mozambique, India and South Africa and randomized to 1HP or 3HP. Median age was 34 years (range, 13-78) and 58% were female. By the composite endpoint, treatment completion was similar in the 1HP and 3HP arms (53.9% vs 56.4%, site-adjusted difference 2.9%, p = 0.49, Figure 1). Treatment completion in the 1HP and 3HP arms, respectively, was 87.0% vs 73.1% (p < 0.001) by self-report; 90.9% vs 91.6% by pill count (p = 0.80); and 59.1% vs 73.1% (p < 0.001) by EMD. Treatment limiting AEs occurred in the 1.6% of participants in the 1HP and 0.4% in the 3HP arm (p = 0.11), and targeted grade ≥2 AEs were similar (2.0% vs.3.56%, p = 0.85). Targeted grade >3 AEs occurred in 0.4% and 0.9%, respectively. There were no hypersensitivity reactions or hepatotoxicity in either arm. Grade 3 or higher AEs attributed to study medications occurred in 1 (0.4%) and 2 (0.8%) participants in the 1HP and 3HP arms, respectively (p = 0.7). No cases of TB were detected in 6 months of follow up.

Conclusion

Treatment completion was similar with 1HP and 3HP among HHCs by the composite endpoint and by pill count but was better by self-report with 1HP and by EMD with 3HP. Our results highlight the challenges of adherence measurement in clinical trials. Both 1HP and 3HP are safe in HIV-negative HHCs and provide patient choice and program flexibility.

This abstract is funded by: Unitaid