长效体抑制剂可以保护免受SHIV的重复感染
Samuel J Vidal1,2, Elena Bekerman3, Derek Hansen3
1Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Nature
|December 7, 2021
概括
在灵长类动物模型中,一种新型小分子HIV囊抑制剂GS- CA1的单剂量提供了长期保护. 这种长效的暴露前预防 (PrEP) 策略在预防艾滋病毒感染方面显得有前途.
科学领域:
- 病毒学
- 免疫学
- 药理学
背景情况:
- 目前没有疫苗可以预防艾滋病毒感染,因此使用抗逆转录病毒药物 (ARV) 进行暴露前预防非常重要.
- 长效抗病毒药物通过减少服用频率而优于每日治疗方案.
- GS- CA1 是一种强大的小分子艾滋病毒囊抑制剂,对各种艾滋病毒菌株有效,包括耐药变种.
研究的目的:
- 评估单次皮下注射GS- CA1对 rhesus macaques中反复出现的人类免疫缺陷病毒 (SHIV) 的长期保护效果.
- 确定药物动力学特征并将药物度与保护相关联.
主要方法:
- rhesus 获得一次性皮下注射 GS- CA1 (300 mg/ kg).
- 在24周内,动物每周重复接受直肠SHIV挑战.
- 进行了药理动力学分析,以测量GS- CA1度,并将其与保护相关联.
主要成果:
- 一次300毫克/ 公斤的GS- CA1可使每次暴露的感染风险在24周内降低97%.
- 所有对照动物在15周的挑战后都被感染了.
- 在该模型中,高于95%有效度的两倍的GS- CA1血水平提供了100%的保护.
结论:
- 在灵长类动物模型中,GS- CA1作为单剂量皮下注射用于HIV暴露前预防的长期疗效.
- 这项研究支持开发HIV囊抑制剂作为一种新的长效PrEP策略.
- 药物动力学数据表明GS- CA1度与对SHIV感染的保护之间存在强烈的相关性.
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