Mulato A S, Cherrington J M
Gilead Sciences, Foster City, CA 94404, USA.
Antiviral Res. 1997 Nov;36(2):91-7. doi: 10.1016/s0166-3542(97)00043-0.
Adefovir (PMEA, 9-(2-phosphonomethoxyethyl)adenine), an acyclic nucleoside phosphonate analogue is active against retroviruses, hepadnaviruses and herpesviruses. Adefovir dipivoxil, an orally bioavailable prodrug of adefovir is currently in phase III clinical trials for the treatment of HIV and phase II clinical trials for the treatment of HBV infections. PMPA (9-(2-phosphonomethoxypropyl)adenine) is a related acyclic nucleoside phosphonate analogue that has demonstrated potent anti-SIV activity in rhesus macaques and recently has shown marked anti-HIV activity in a phase I clinical study. Since the standard of care for AIDS patients has become combination therapy, the effects of other antiretroviral compounds (d4T, ddC, AZT, ddI, 3TC, nelfinavir, ritonavir, indinavir, and saquinavir) on the anti-HIV activity of adefovir and PMPA were investigated in vitro. Adefovir and PMPA both demonstrated strong synergistic anti-HIV activity in combination with AZT. Adefovir demonstrated minor to moderate synergistic inhibition of HIV replication in combination with PMPA, d4T, ddC, nelfinavir, ritonavir, and saquinavir. PMPA demonstrated minor synergistic inhibition of HIV replication in combination with ddI and nelfinavir (and adefovir). All other combinations showed additive inhibition of HIV replication in vitro. Importantly, no antagonistic interactions were measured for any of the adefovir or PMPA combinations.
阿德福韦（PMEA，9 -（2 - 膦酰甲氧基乙基）腺嘌呤），一种无环核苷膦酸酯类似物，对逆转录病毒、嗜肝DNA病毒和疱疹病毒具有活性。阿德福韦酯，阿德福韦的一种口服生物利用度前药，目前正处于治疗HIV的III期临床试验和治疗HBV感染的II期临床试验阶段。PMPA（9 -（2 - 膦酰甲氧基丙基）腺嘌呤）是一种相关的无环核苷膦酸酯类似物，已在恒河猴中显示出有效的抗SIV活性，并且最近在一项I期临床研究中显示出显著的抗HIV活性。由于艾滋病患者的标准治疗已成为联合治疗，因此在体外研究了其他抗逆转录病毒化合物（d4T、ddC、AZT、ddI、3TC、奈非那韦、利托那韦、茚地那韦和沙奎那韦）对阿德福韦和PMPA抗HIV活性的影响。阿德福韦和PMPA与AZT联合使用时均表现出强大的协同抗HIV活性。阿德福韦与PMPA、d4T、ddC、奈非那韦、利托那韦和沙奎那韦联合使用时，对HIV复制表现出轻微至中度的协同抑制作用。PMPA与ddI和奈非那韦（以及阿德福韦）联合使用时，对HIV复制表现出轻微的协同抑制作用。所有其他组合在体外均表现出对HIV复制的相加抑制作用。重要的是，对于任何阿德福韦或PMPA组合，均未检测到拮抗相互作用。
