One-Month Rifapentine plus Isoniazid (1HP) is a safe regimen for LTBI treatment in non-HIV population: A randomized controlled trial

<bold>Background:</bold> The 3HP regimen—weekly rifapentine plus isoniazid for 12 doses—improves the completion rate of latent tuberculosis infection (LTBI) treatment, but flu-like symptoms are common. The new 1HP regimen—daily rifapentine plus isoniazid for 28 days—has low toxicity in HIV-infected populations. However, its safety profiles in non-HIV population remains unclear. Method: This randomised, multicentre trial compared the completion rate and risks of adverse drug reactions and systemic drug reactions (SDRs) of 1HP and 3HP in ≥13-year-old non-HIV subjects with LTBI between September 2019 and July 2023. We also investigated the associations between SDRs and plasma levels of drugs and their metabolites. <bold>Results:</bold> A total of 251 and 239 individuals (Figure 1) were randomised into 1HP and 3HP groups, respectively, with completion rates of 82.9% and 84.5%, respectively. Among them, 12.7% and 10.9% of 3HP group experienced SDRs, respectively (p=0.522): predominantly urticaria in 1HP group (59.4%) and flu-like syndrome in 3HP group (80.8%). Among participants experiencing SDRs, 43.8% and 34.6% in 1HP and 3HP groups, respectively, completed treatment (p=0.470). Cutaneous reactions were more common with 1HP (32.7% vs. 13.0%, p<0.001). In the 1HP group, a higher plasma desacetyl-rifapentine level at both 2h and 6h after dosing was associated with urticaria (p=0.018 and p=0.047, respectively). <bold>Conclusion:</bold> In non-HIV population, the 1HP group had a similar completion rate and risk of SDR with 3HP group. Urticaria, rather than flu-like syndrome, is the predominant presentation of 1HP-related SDR. 1HP can be safely applied in non-HIV population.