一个月每日和三个月每周利福喷丁加异烟肼治疗非 HIV 人群潜伏性结核感染的完成率和安全性相当：一项随机对照试验。
One-month daily and three-month weekly rifapentine plus isoniazid are comparable in completion rate and safety for latent tuberculosis infection in non-HIV Population: a randomized controlled trial.
机构信息
Department of Internal Medicine, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; School of Medicine, Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
Department of Internal Medicine, National Taiwan University Hospital, Hsinchu Branch, Hsinchu, Taiwan; Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; National Taiwan University, College of Medicine, Taipei, Taiwan.
出版信息
Clin Microbiol Infect. 2024 Nov;30(11):1410-1417. doi: 10.1016/j.cmi.2024.06.024. Epub 2024 Jul 10.
OBJECTIVES
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.
DISCUSSION
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%.
目的
每周利福喷丁加异烟肼治疗 3 个月（3HP）可提高潜伏性结核感染治疗的完成率，但常伴有流感样症状。新型 1HP 方案，涉及每日利福喷丁加异烟肼治疗 28 天，在 HIV 感染者中显示出低毒性。我们旨在研究在非 HIV 人群中，1HP 是否比 3HP 治疗期间全身药物反应（SDR）的发生率更低。
方法
这项随机、多中心试验比较了 2019 年 9 月至 2023 年 9 月期间年龄≥13 岁的潜伏性结核感染的非 HIV 受试者中，1HP 和 3HP 的完成率和 SDR 风险（ClinicalTrials.gov：NCT04094012）。我们还研究了 SDR 与药物及其代谢物的血浆水平之间的关系。
结果
共有 251 名和 239 名受试者分别随机分配至 1HP 和 3HP 组，完成率分别为 82.9%（208/251）和 84.5%（202/239）。其中，12.7%（32/251）和 10.9%（26/239）的 1HP 和 3HP 组发生 SDR，分别为（p 0.522），1HP 组主要为荨麻疹（59.4%[19/32]），3HP 组为流感样综合征（80.8%[21/26]）。在发生 SDR 的参与者中，1HP 和 3HP 组分别有 43.8%（14/32）和 34.6%（9/26）完成治疗（p 0.470）。1HP 组的皮肤反应比 3HP 组更常见（32.7%[82/251] vs. 13.0%[31/239]，p < 0.001）。在 1HP 组中，荨麻疹与给药后 2 小时（中位数[四分位数范围]：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]，p 0.047）时的血浆去乙酰利福平水平较高有关。
讨论
在非 HIV 人群中，1HP 下 SDR 的发生率并不低于 3HP。值得注意的是，荨麻疹而非流感样综合征是与 1HP 相关的主要 SDR。这项研究的结果强调了 1HP 方案在完成率超过 80%的非 HIV 人群中的可行性。
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