Fixed-Dose Rifapentine-Isoniazid (1HP) for Tuberculosis Preventive Treatment in Chinese Adults: A Prospective Real-World Safety and Pharmacokinetic Study.

Abstract

The World Health Organization recommends one month of daily rifapentine plus isoniazid (1HP) for tuberculosis preventive treatment (TPT). Real-world safety and feasibility data remain scarce, particularly for East Asian populations, and the performance of fixed-dose 1HP in routine clinical practice requires prospective evaluation. We conducted a prospective study at a tuberculosis referral center in Shenzhen, China, enrolling 136 non-HIV adults (body weight 42-90 kg) with tuberculosis infection between October 2024 and July 2025. All participants received fixed-dose1HP. Outcomes included treatment completion (defined as taking ≥ 23 doses within 40 days), adverse events graded by CTCAE v5.0, and 12-hour post-dose rifapentine concentrations measured by LC-MS/MS. Treatment completion reached 76.5% (104/136; 95% CI, 68.7-82.8%). Adverse events occurred in 26.5% of participants, most commonly neutropenia (14.7%) and rash (6.6%); grade ≥3 events were observed in only 1.5% (2/136), both in patients receiving concurrent methotrexate. Median rifapentine concentration was 21.8 mg/L (IQR, 14.8-28.4), and 91.9% of participants exceeded the model-informed 10 mg/L threshold. Body weight demonstrated a modest inverse correlation with rifapentine concentrations (ρ = -0.24; P = .005), accounting for only 7.1% of interindividual variability. Fixed-dose 1HP exhibited good tolerability and achieved acceptable completion rate in Chinese adult population. Pharmacokinetic results confirmed adequate rifapentine exposure across the studied weight range, lending support to fixed-dose 1HP for programmatic scale-up.