匹伐他汀联合用药体外抗HIV-1活性研究

The Combined Anti-HIV-1 Effects of Pitavastatin and Antiviral Drugs in vitro

目的研究他汀类药物体外抗人类免疫缺陷病毒I型(human immunodeficiency virus type 1,HIV-1)活性并评价匹伐他汀与其它抗HIV药物联合使用时的抗病毒活性。方法采用噻唑蓝(MTT)比色法测定他汀类药物对C8166细胞的毒性作用;合胞体计数检测他汀类药物对实验株HIV-1_(IIIB)诱导C8166细胞病变的抑制作用;酶联免疫吸附测定法(ELISA)测定HIV-1 p24抗原检测他汀类药物对实验株HIV-1_(IIIB)急性感染C8166细胞中病毒复制的抑制作用以及匹伐他汀与其它抗HIV药物联合用药的联合效应。结果他汀类药物中匹伐他汀具有显著体外抗HIV-1活性,匹伐他汀与核苷类逆转录酶抑制剂(替诺福韦、恩曲他滨、拉米夫定、齐多夫定)和蛋白酶抑制剂(茚地那韦和达芦那韦)联合用药时,药物间呈现协同作用;与非核苷类逆转录酶抑制剂(依曲韦林)联合用药时,药物间呈现拮抗作用;与整合酶链转移抑制剂(雷特格韦和度鲁特韦)联合用药时,药物间呈现相加作用。结论匹伐他汀除与依曲韦林联合时药物间呈现拮抗作用外,与其它抗HIV药物联用均呈现相加或协同作用。

Objective To investigate the in vitro anti-HIV-1 activity of statins and to evaluate the antiviral of pitavastatin in combination with other anti-HIV drugs.Methods The cytotoxicity of statins on C8166 cells was determined using the MTT assay.The inhibitory effect of statins on HIV-1_(IIIB)-induced cytopathic effect was measured by counting the number of syncytia.The inhibitory effect of statins on the viral replication in C8166 cells acutely infected with laboratory-adapted strains HIV-1_(IIIB) was detected by ELISA.The combination of pitavastatin and anti-HIV drugs with the different targets was measured by ELISA.Results Among statins,pivastatin has significant anti-HIV-1 activity in vitro.The combination of pivastatin with nucleoside reverse transcriptase inhibitors(tenofovir,emtricitabine,lamivudine and zidovudine)and protease inhibitors(indinavir and darunavir)showed synergistic effect.The combination of pivastatin with non-nucleoside reverse transcriptase inhibitor(etravirine)showed antagonism effect.The combination of pivastatin with integrase strand transfer inhibitors(raltegravir and dolutegravir)showed additive effect.Conclusion Pitavastatin showed synergistic or additive effects when combined with other anti-HIV drugs, except for antagonism when combined with etravirine.