Palmer S, Margot N, Gilbert H, Shaw N, Buckheit R, Miller M
HIV Drug Resistance Program, National Cancer Institute, National Institutes of Health, Frederick, Maryland 21702-1201, USA.
AIDS Res Hum Retroviruses. 2001 Aug 10;17(12):1167-73. doi: 10.1089/088922201316912772.
New antiretroviral drugs with activity against strains of human immunodeficiency virus type 1 (HIV-1) with non-B subtypes and with resistance to current antiretroviral drugs are needed. The activity of two nucleotide analogs, tenofovir and adefovir (PMPA and PMEA, respectively), against non-B subtypes and nucleoside-resistant primary HIV-1 isolates was assessed. Tenofovir and adefovir were fully active against a panel of subtypes A, C, D, E, F, G, and group O primary HIV-1 isolates as compared with their respective activity against subtype B isolates. Moreover, the susceptibility of a panel of 10 primary HIV-1 isolates with >10-fold mean resistance to zidovudine, lamivudine, and abacavir was within 2.2-fold of wild-type tenofovir susceptibility for each isolate. An oral prodrug of tenofovir, tenofovir disoproxil fumarate (DF), is currently in phase III clinical trials for the treatment of HIV-1 infection. These in vitro susceptibility results suggest that tenofovir DF may be active in vivo against HIV-1 with nucleoside resistance as well as against HIV-1 with non-B subtypes.
需要有抗1型人类免疫缺陷病毒（HIV-1）非B亚型毒株及对现有抗逆转录病毒药物耐药毒株活性的新型抗逆转录病毒药物。评估了两种核苷酸类似物替诺福韦和阿德福韦（分别为PMPA和PMEA）对非B亚型及核苷类耐药的HIV-1原始分离株的活性。与它们对B亚型分离株的各自活性相比，替诺福韦和阿德福韦对A、C、D、E、F、G亚型及O组HIV-1原始分离株均具有完全活性。此外，一组对齐多夫定、拉米夫定和阿巴卡韦平均耐药>10倍的10株HIV-1原始分离株，每株对替诺福韦的敏感性与野生型相比均在2.2倍以内。替诺福韦的口服前体药物富马酸替诺福韦二吡呋酯（DF）目前正处于治疗HIV-1感染的III期临床试验阶段。这些体外敏感性结果表明，富马酸替诺福韦二吡呋酯在体内可能对核苷类耐药的HIV-1以及非B亚型的HIV-1具有活性。
