Chong Yong, Kawai Naoki, Tani Naoki, Bando Takuma, Takasaki Yoshio, Shindo Shizuo, Ikematsu Hideyuki
Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences (The First Department of Internal Medicine), Fukuoka, Japan.
Japan Physicians Association, Tokyo, Japan; Kawai Clinic, Gifu, Japan.
Antiviral Res. 2021 Aug;192:105092. doi: 10.1016/j.antiviral.2021.105092. Epub 2021 May 27.
Although the virological and clinical efficacies of baloxavir for influenza and the post-treatment emergence of variant viruses have been reported in clinical trials, its efficacies have not been fully investigated in clinical settings. This prospective, observational investigator-initiated study was conducted during the 2019-2020 Japanese influenza season. In outpatients receiving baloxavir or oseltamivir, nasopharyngeal samples were obtained on day 1 before treatment and on the scheduled days 5 and 10 after treatment. RT-PCR and sequencing were performed to detect polymerase acidic protein (PA) E23X/I38X and neuraminidase (NA) H275Y variants in clinical and cultivated samples. Fever and illness-related symptoms were recorded using self-reporting diaries. Overall, 116 outpatients, 76 treated with baloxavir (34 under 12 years) and 40 with oseltamivir (32 under 12 years), were eligible. Of these, 91 were infected with A (H1N1)pdm09 (78.4%), of which 58 received baloxavir and 33 received oseltamivir. PA variants were detected in clinical (1.7%, 1/58; 3.8%, 1/26 for children under 12 years) and isolated (3.4%, 2/58; 3.8%, 1/26 for children under 12 years) samples obtained on day 5 after baloxavir treatment, but not on day 10. The isolation frequencies of A (H1N1)pdm09 on days 5 and 10 after baloxavir treatment were 5.2% (3/58) and 0.0% (0/58), respectively. Of the three viruses isolated on day 5, two (66.7%, 2/3) were PA I38 T/F variants with reduced baloxavir susceptibility. The isolation frequencies of A (H1N1)pdm09 on days 5 and 10 after oseltamivir treatment were 30.3% (10/33) and 6.1% (2/33), respectively. Only the two viruses isolated on day 10 were NA H275Y variants. The median duration of fever in baloxavir and oseltamivir recipients was 22.3 and 27.5 h, respectively. No patients with PA or NA variants showed prolonged durations of fever. Baloxavir was virologically effective for influenza in the clinical setting of the 2019-2020 Japanese season. Variant emergence after baloxavir treatment was limited to the early post-treatment stage.
虽然在临床试验中已报告了巴洛沙韦治疗流感的病毒学和临床疗效以及治疗后变异病毒的出现情况，但其疗效在临床环境中尚未得到充分研究。这项前瞻性、观察性的研究者发起的研究于2019 - 2020年日本流感季节进行。在接受巴洛沙韦或奥司他韦治疗的门诊患者中，于治疗前第1天以及治疗后预定的第5天和第10天采集鼻咽样本。进行逆转录聚合酶链反应（RT-PCR）和测序，以检测临床样本和培养样本中的聚合酶酸性蛋白（PA）E23X/I38X和神经氨酸酶（NA）H275Y变异体。使用自我报告日记记录发热及与疾病相关的症状。总体而言，116名门诊患者符合条件，其中76名接受巴洛沙韦治疗（34名年龄在12岁以下），40名接受奥司他韦治疗（32名年龄在12岁以下）。其中，91名感染了甲型（H1N1）pdm09（78.4%），其中58名接受巴洛沙韦治疗，33名接受奥司他韦治疗。在巴洛沙韦治疗后第5天采集的临床样本（1.7%，1/58；12岁以下儿童为3.8%，1/26）和分离样本（3.4%，2/58；12岁以下儿童为3.8%，1/26）中检测到PA变异体，但在第10天未检测到。巴洛沙韦治疗后第5天和第10天甲型（H1N1）pdm09的分离频率分别为5.2%（3/58）和0.0%（0/58）。在第5天分离出的三种病毒中，两种（66.7%，2/3）是对巴洛沙韦敏感性降低的PA I38T/F变异体。奥司他韦治疗后第5天和第10天甲型（H1N1）pdm09的分离频率分别为30.3%（10/33）和6.1%（2/33）。仅在第10天分离出的两种病毒是NA H275Y变异体。接受巴洛沙韦和奥司他韦治疗的患者发热的中位持续时间分别为22.3小时和27.5小时。没有PA或NA变异体的患者发热持续时间延长。在2019 - 2020年日本流感季节的临床环境中，巴洛沙韦对流感具有病毒学疗效。巴洛沙韦治疗后变异体的出现仅限于治疗后的早期阶段。
