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普瑞替韦治疗一名感染艾滋病毒者的核苷类似物耐药性唇疱疹单纯疱疹病毒2感染

Pritelivir for the Treatment of Nucleoside Analogue-Resistant Orolabial Herpes Simplex Virus 2 in a Person Living with HIV.

作者信息

Purssell Andrew, Leung Kennedy, Giguère Pierre, Angel Jonathan B

机构信息

Division of Infectious Diseases, Department of Medicine, University of Ottawa, Ottawa, Canada.

Ottawa Hospital Research Institute, Ottawa, Canada.

出版信息

J Assoc Med Microbiol Infect Dis Can. 2024 Jun 12;9(2):108-112. doi: 10.3138/jammi-2023-0028. eCollection 2024 Jun.

Abstract

BACKGROUND

Nucleoside analogue-resistant herpes simplex virus infections are increasingly observed especially in immunocompromised patients. Currently, other options for treatment such as foscarnet and cidofovir are limited by difficulty of administration and significant risk of toxicity. Our report describes use of pritelivir, a novel helicase-primase inhibitor, in the treatment of nucleoside analogue-refractory orolabial HSV-2 infection.

METHODS

In 2017, a 53-year-old male with HIV on therapy presented with swelling of the right upper lip and a solid lesion inferior to the right nostril. Biopsy revealed cytopathic effects and immunohistochemistry staining confirming herpes simplex virus infection. The patient received multiple treatment courses including nucleoside analogue therapy, topical and intravenous foscarnet and cidofovir, and topical imiquimod but these failed to establish a significant and durable therapeutic response.

RESULTS

A swab of the lesion tested positive for HSV-2 via PCR. Subsequent genotyping revealed a M183X mutation in expected to convey resistance to acyclovir and penciclovir. The patient was started on oral pritelivir 400 mg once followed by 100 mg daily for 27 days, obtained through Health Canada's Special Access Program, resulting in near complete resolution of the lesion.

CONCLUSION

Pritelivir is a novel helicase-primase inhibitor that appears to be an attractive option for management of resistant herpes simplex infections due to its unique mechanism, excellent oral bioavailability, and minimal toxicity. To our knowledge, this is the first described case of treatment of nucleoside analogue-resistant orolabial herpes simplex 2 infection with pritelivir and the first documented use of pritelivir in Canada.

摘要

背景

核苷类似物耐药的单纯疱疹病毒感染日益常见,尤其是在免疫功能低下的患者中。目前,其他治疗选择,如膦甲酸钠和西多福韦,受到给药困难和显著毒性风险的限制。我们的报告描述了新型解旋酶-引物酶抑制剂普瑞替韦用于治疗核苷类似物难治性唇疱疹HSV-2感染的情况。

方法

2017年,一名接受治疗的53岁HIV男性患者出现右上唇肿胀及右鼻孔下方实性病变。活检显示细胞病变效应,免疫组化染色证实为单纯疱疹病毒感染。该患者接受了多个疗程的治疗,包括核苷类似物治疗、局部和静脉注射膦甲酸钠及西多福韦,以及局部应用咪喹莫特,但均未能建立显著且持久的治疗反应。

结果

病变拭子经PCR检测HSV-2呈阳性。随后的基因分型显示存在M183X突变,预计对阿昔洛韦和喷昔洛韦耐药。通过加拿大卫生部的特殊准入计划,该患者开始口服普瑞替韦,首剂400 mg,随后每日100 mg,共27天,病变几乎完全消退。

结论

普瑞替韦是一种新型解旋酶-引物酶抑制剂,由于其独特的作用机制、出色的口服生物利用度和最小的毒性,似乎是治疗耐药单纯疱疹感染的一个有吸引力的选择。据我们所知,这是首例用普瑞替韦治疗核苷类似物耐药性唇疱疹单纯疱疹病毒2感染的病例,也是加拿大首次记录使用普瑞替韦的病例。

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