普瑞巴林治疗单纯疱疹病毒 2 型感染的临床研究进展

Helicase-primase inhibitor pritelivir for HSV-2 infection.

机构信息

From the University of Washington and Fred Hutchinson Cancer Research Center, Seattle (A.W., L.C., A.M., C.J., M.-L.H., S. Selke); AiCuris, Wuppertal, Germany (B.T., S. Stoelben, H.-P.S., H.R.-S., A.B.); Westover Heights Clinic, Portland, OR (T.W.); University of Texas, Houston (S.T.); University of Utah, Salt Lake City (J.K.); Indiana University School of Medicine, Indianapolis (K.F.); and Cetero Research, Miami (L.G.).

出版信息

N Engl J Med. 2014 Jan 16;370(3):201-10. doi: 10.1056/NEJMoa1301150.

DOI:10.1056/NEJMoa1301150

PMID:24428466

Abstract

BACKGROUND

Pritelivir, an inhibitor of the viral helicase-primase complex, exhibits antiviral activity in vitro and in animal models of herpes simplex virus (HSV) infection. We tested the efficacy and safety of pritelivir in otherwise healthy persons with genital HSV-2 infection.

METHODS

We randomly assigned 156 HSV-2-positive persons with a history of genital herpes to receive one of four doses of oral pritelivir (5, 25, or 75 mg daily, or 400 mg weekly) or placebo for 28 days. Participants obtained daily swabs from the genital area for HSV-2 testing, which was performed with a polymerase-chain-reaction assay. Participants also maintained a diary of genital signs and symptoms. The primary end point was the rate of genital HSV shedding.

RESULTS

HSV shedding among placebo recipients was detected on 16.6% of days; shedding among pritelivir recipients was detected on 18.2% of days among those receiving 5 mg daily, 9.3% of days among those receiving 25 mg daily, 2.1% of days among those receiving 75 mg daily, and 5.3% of days among those receiving 400 mg weekly. The relative risk of viral shedding with pritelivir, as compared with placebo, was 1.11 (95% confidence interval [CI], 0.65 to 1.87) with the 5-mg daily dose, 0.57 (95% CI, 0.31 to 1.03) with the 25-mg daily dose, 0.13 (95% CI, 0.04 to 0.38) with the 75-mg daily dose, and 0.32 (95% CI, 0.17 to 0.59) with the 400-mg weekly dose. The percentage of days with genital lesions was also significantly reduced, from 9.0% in the placebo group to 1.2% in both the group receiving 75 mg of pritelivir daily (relative risk, 0.13; 95% CI, 0.02 to 0.70) and the group receiving 400 mg weekly (relative risk, 0.13; 95% CI, 0.03 to 0.52). The rate of adverse events was similar in all groups.

CONCLUSIONS

Pritelivir reduced the rates of genital HSV shedding and days with lesions in a dose-dependent manner in otherwise healthy men and women with genital herpes. (Funded by AiCuris; ClinicalTrials.gov number, NCT01047540.).

摘要

背景

普瑞巴林是一种病毒解旋酶-引发酶复合物抑制剂，在单纯疱疹病毒（HSV）感染的体外和动物模型中均显示出抗病毒活性。我们在患有生殖器单纯疱疹病毒 2 型（HSV-2）感染的健康人中测试了普瑞巴林的疗效和安全性。

方法

我们随机分配了 156 名 HSV-2 阳性且有生殖器疱疹病史的患者，他们分别接受了四种剂量的口服普瑞巴林（每天 5、25 或 75 毫克，或每周 400 毫克）或安慰剂，疗程为 28 天。参与者每天从生殖器部位获得用于 HSV-2 检测的拭子，该检测采用聚合酶链反应检测。参与者还保留了生殖器体征和症状的日记。主要终点是生殖器 HSV 脱落率。

结果

安慰剂组中生殖器 HSV 脱落的检出率为 16.6%；接受 5 毫克/天普瑞巴林治疗的患者中生殖器脱落的检出率为 18.2%，接受 25 毫克/天普瑞巴林治疗的患者中生殖器脱落的检出率为 9.3%，接受 75 毫克/天普瑞巴林治疗的患者中生殖器脱落的检出率为 2.1%，接受 400 毫克/周普瑞巴林治疗的患者中生殖器脱落的检出率为 5.3%。与安慰剂相比，普瑞巴林的病毒脱落相对风险分别为：5 毫克/天剂量为 1.11（95%置信区间[CI]，0.65 至 1.87），25 毫克/天剂量为 0.57（95%CI，0.31 至 1.03），75 毫克/天剂量为 0.13（95%CI，0.04 至 0.38），400 毫克/周剂量为 0.32（95%CI，0.17 至 0.59）。生殖器病变的天数也明显减少，安慰剂组为 9.0%，接受 75 毫克普瑞巴林/天治疗的患者（相对风险，0.13；95%CI，0.02 至 0.70）和接受 400 毫克/周普瑞巴林治疗的患者（相对风险，0.13；95%CI，0.03 至 0.52）分别为 1.2%。各组不良反应发生率相似。