HIV-1初始传播病毒药物敏感性研究  

The sensitivity of transmitted/founder HIV-1 to anti-HIV drugs

作　　者：丁寄葳[1] 赵建元[1,2] 米泽云 魏涛[2] 岑山[1] 

机构地区：[1]中国医学科学院北京协和医学院医药生物技术研究所,北京100050 [2]北京联合大学应用文理学院,北京100192

出　　处：《药学学报》2016年第3期367-372,共6页Acta Pharmaceutica Sinica

基　　金：国家自然科学基金委员会-加拿大国立卫生研究院研究基金课题(CIHR)合作基金资助项目(81361128017)

摘　　要：人类免疫缺陷病毒(human immunodeficiency virus type 1,HIV-1)黏膜感染绝大多数由一个或者少数几个病毒建立并最终发展为系统感染,上述病毒称为初始传播病毒(transmitted/founder virus,T/F病毒)。研究T/F病毒对不同抗HIV-1药物的敏感性,可为艾滋病高危人群提供优化的暴露前预防性治疗(pre-exposure prophylaxis,Pr EP)策略。本文首先构建了含荧光素酶报告基因的T/F病毒单轮感染系统,进而分析比较了长期感染病毒和T/F病毒对不同抗HIV-1药物的敏感性。实验结果显示,与同一亚型的长期感染病毒相比,T/F病毒对HIV-1核苷类逆转录酶抑制剂(nucleoside reverse transcriptase inhibitors,NRTIs)、整合酶抑制剂(integrase inhibitors,INIs)及蛋白酶抑制剂(protease inhibitors,PIs)的敏感性并没有表现出显著性差异(P>0.05),而对非核苷类逆转录酶抑制剂(non-nucleoside reverse transcriptase inhibitors,NNRTIs)表现出一定的耐药性,IC50显著提高(P<0.05)。这一结果提示,对于艾滋病高危人群的暴露前预防性治疗应避免选择NNRTIs。The majority of mucosal HIV-1 infection is initially established by a few HIV-1 viral variants, followed by the development of overt systemic infection, and these viral variants are known as transmitted/ founder viruses（T/F viruses）. Investigation of the sensitivity of T/F virus to different anti-HIV-1 drugs will provide the best strategies of pre-exposure prophylaxis（Pr EP） for high-risk groups of HIV-infected patients. Herein we constructed for the first time, a luciferase reporter system for HIV-1 T/F viruses, and then compared the drug sensitivity between T/F viruses and chronic infection virus. The result showed that the 50% inhibitory concentration（IC50） of nucleoside reverse transcriptase inhibitors（NRTIs）, integrase inhibitors（INIs） and protease inhibitors（PIs） were not significantly different between the T/F viruses and chronic infection viruses of the same subtype（P 0.05）, while non-nucleoside reverse transcriptase inhibitors（NNRTIs） showed a moderate resistance to T/F viruses, with a significant increase in IC50（P 0.05）. The conclusion suggests that when patients are in high-risk or in the acute infection of HIV-1, NNRTIs should be avoided in the first-line antiretroviral therapy regimens.

关 键 词：HIV-1 暴露前预防性治疗 初始传播病毒 报告基因 抗HIV-1药物 

分 类 号：R966[医药卫生—药理学]