Abstract：
OBJECTIVE: The weekly rifapentine plus isoniazid for 3 months (3HP) improves completion rate of latent tuberculosis infection treatment, but flu-like symptoms are common. The novel 1HP regimen, involving daily rifapentine plus isoniazid for 28 days, has demonstrated low toxicity in HIV-infected populations. We aimed to investigate whether 1HP has a lower incidence rate of systemic drug reaction (SDR) compared with 3HP during treatment in non-HIV populations.
METHODS: This randomized, multicentre trial compared the completion rate and risks of SDRs of 1HP and 3HP in aged ≥13 years non-HIV subjects with latent tuberculosis infection between September 2019 and September 2023 (ClinicalTrials.gov: NCT04094012). We also investigated associations between SDRs and plasma levels of drugs and their metabolites.
RESULTS: A total of 251 and 239 individuals were randomly assigned to 1HP and 3HP groups, respectively, with completion rates of 82.9% (208/251) and 84.5% (202/239), respectively. Among them, 12.7% (32/251) and 10.9% (26/239) of 1HP and 3HP groups experienced SDRs, respectively (p 0.522), predominantly urticaria in 1HP group (59.4% [19/32]) and flu-like syndrome in 3HP group (80.8% [21/26]). Among participants experiencing SDRs, 43.8% (14/32) and 34.6% (9/26) in 1HP and 3HP groups, respectively, completed treatment (p 0.470). Cutaneous reactions were more common in 1HP than 3HP group (32.7% [82/251] vs. 13.0% [31/239], p < 0.001). In 1HP group, urticaria was associated with a higher plasma desacetyl-rifapentine level (ug/mL) at both 2 (median [interquartile range]: 36.06 [17.46-50.79] vs. 22.94 [14.67-31.65], p 0.018) and 6 hours (26.13 [15.80-53.06] vs. 29.83 [18.13-34.01], p 0.047) after dosing.
CONCLUSIONS: In non-HIV population, the incidence rate of SDR under 1HP is not lower than 3HP. Notably, urticaria, rather than flu-like syndrome, was the predominant SDR associated 1HP. The findings of this study underscore the feasibility of 1HP regimen in non-HIV populations with a high-completion rate exceeding 80%.
METHODS: This randomized, multicentre trial compared the completion rate and risks of SDRs of 1HP and 3HP in aged ≥13 years non-HIV subjects with latent tuberculosis infection between September 2019 and September 2023 (ClinicalTrials.gov: NCT04094012). We also investigated associations between SDRs and plasma levels of drugs and their metabolites.
RESULTS: A total of 251 and 239 individuals were randomly assigned to 1HP and 3HP groups, respectively, with completion rates of 82.9% (208/251) and 84.5% (202/239), respectively. Among them, 12.7% (32/251) and 10.9% (26/239) of 1HP and 3HP groups experienced SDRs, respectively (p 0.522), predominantly urticaria in 1HP group (59.4% [19/32]) and flu-like syndrome in 3HP group (80.8% [21/26]). Among participants experiencing SDRs, 43.8% (14/32) and 34.6% (9/26) in 1HP and 3HP groups, respectively, completed treatment (p 0.470). Cutaneous reactions were more common in 1HP than 3HP group (32.7% [82/251] vs. 13.0% [31/239], p < 0.001). In 1HP group, urticaria was associated with a higher plasma desacetyl-rifapentine level (ug/mL) at both 2 (median [interquartile range]: 36.06 [17.46-50.79] vs. 22.94 [14.67-31.65], p 0.018) and 6 hours (26.13 [15.80-53.06] vs. 29.83 [18.13-34.01], p 0.047) after dosing.
CONCLUSIONS: In non-HIV population, the incidence rate of SDR under 1HP is not lower than 3HP. Notably, urticaria, rather than flu-like syndrome, was the predominant SDR associated 1HP. The findings of this study underscore the feasibility of 1HP regimen in non-HIV populations with a high-completion rate exceeding 80%.
摘要：
目的：3HP方案，由12剂每周利福喷丁加异烟肼组成，提高潜伏性结核感染（LTBI）治疗的完成率，但是流感样症状很常见。新的1HP方案，每天服用利福喷丁加异烟肼28天，在人类免疫缺陷病毒（HIV）感染人群中已证明低毒性。我们的目的是调查在非HIV人群治疗期间，与3HP相比，1HP是否具有更低的全身药物反应（SDR）发生率。
方法：这是随机的，多中心试验比较了2019年9月至2023年9月期间，年龄≥13岁的非HIV感染者中1HP和3HP的SDR完成率和风险（ClinicalTrials.gov：NCT04012）。我们还调查了SDR与药物及其代谢物的血浆水平之间的关联。
结果：总共251和239个人被随机分为1HP和3HP组，分别,完成率为82.9%(208/251)和84.5%(202/239)，分别。其中,12.7%（32/251）和10.9%（26/239）的1HP和3HP组经历了特别提款权，分别(p=0.522)，1HP组主要为荨麻疹(59.4%[19/32]),3HP组主要为流感样综合征(80.8%[21/26])。在经历特别提款权的参与者中，1HP和3HP组的43.8%(14/32)和34.6%(9/26),分别,完成治疗（p=0.470）。皮肤反应在1HP组比3HP组更常见(32.7%[82/251]vs.13.0%[31/239]，p<0.001)。在1HP组中，荨麻疹与较高的血浆脱乙酰-利福喷丁水平（ug/mL）在两个2（中位数[四分位距]：36.06[17.46-50.79]vs.22.94[14.67-31.65],p=0.018）和6小时（26.13[15.80-53.06]vs.29.83[18.13-34.01],给药后p=0.047)。
结论：在非HIV人群中，1HP下SDR的发生率不低于3HP。值得注意的是,荨麻疹,而不是流感样综合征，是与1HP相关的主要SDR。这项研究的结果强调了1HP方案在非HIV人群中的可行性，高完成率超过80％。
方法：这是随机的，多中心试验比较了2019年9月至2023年9月期间，年龄≥13岁的非HIV感染者中1HP和3HP的SDR完成率和风险（ClinicalTrials.gov：NCT04012）。我们还调查了SDR与药物及其代谢物的血浆水平之间的关联。
结果：总共251和239个人被随机分为1HP和3HP组，分别,完成率为82.9%(208/251)和84.5%(202/239)，分别。其中,12.7%（32/251）和10.9%（26/239）的1HP和3HP组经历了特别提款权，分别(p=0.522)，1HP组主要为荨麻疹(59.4%[19/32]),3HP组主要为流感样综合征(80.8%[21/26])。在经历特别提款权的参与者中，1HP和3HP组的43.8%(14/32)和34.6%(9/26),分别,完成治疗（p=0.470）。皮肤反应在1HP组比3HP组更常见(32.7%[82/251]vs.13.0%[31/239]，p<0.001)。在1HP组中，荨麻疹与较高的血浆脱乙酰-利福喷丁水平（ug/mL）在两个2（中位数[四分位距]：36.06[17.46-50.79]vs.22.94[14.67-31.65],p=0.018）和6小时（26.13[15.80-53.06]vs.29.83[18.13-34.01],给药后p=0.047)。
结论：在非HIV人群中，1HP下SDR的发生率不低于3HP。值得注意的是,荨麻疹,而不是流感样综合征，是与1HP相关的主要SDR。这项研究的结果强调了1HP方案在非HIV人群中的可行性，高完成率超过80％。
