Background
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 are limited. We compared safety and treatment completion of self-administered 1HP and 3HP among PWH virally suppressed on dolutegravir-based ART.
Methods
The One-to-Three trial was a multi-country, randomized, open-label, phase IV trial that enrolled PWH ≥13 years old without active TB disease and taking ART. Participants were randomized 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 outcomes were completion of ≥90% of doses using a composite of the three treatment completion measures or each measure separately, treatment limiting adverse effects (AEs), ≥Grade 2 targeted AEs, and ≥Grade 3 related AEs. Enrollment began in July 2023 and follow-up ended in July 2025.
Results
500 PWH were enrolled in India (n=250) and South Africa (n=250) and equally randomized to 1HP or 3HP. Median age was 43 years (range, 13-73), 68% were female, and median CD4 count was 790 and 809 cells/mm3 in 1HP and 3HP arms, respectively. All participants had VL <50 copies/mL. By the composite endpoint, treatment completion was lower in the 1HP versus 3HP arm (75.6% vs 87.6%, p<0.001, Figure 1). Treatment completion by self-report or pill count was ≥90% in both groups, but the EMD data showed lower device openings by 1HP versus 3HP participants (79.2% vs 96.4%, p<0.001). Treatment limiting AEs were more common in the 1HP arm than the 3HP arm (3.2% vs 0%, p=0.002), but targeted grade ≥2 AEs were similar (10% vs. 9.6%, p=0.4). 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.
Conclusions
The composite treatment completion was lower and treatment limiting AEs were more common with 1HP vs 3HP among PWH, though treatment completion of both 1HP and 3HP based on self-report or pill count were ≥90%. EMD may underestimate true treatment completion among those taking daily TPT. 1HP and 3HP are safe and provide patient choice and program flexibility.
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