McGill University AIDS Centre, Lady Davis Institute-Jewish General Hospital, Canada.
AIDS. 2010 Sep 10;24(14):2171-9. doi: 10.1097/QAD.0b013e32833cf265.
Because of high intersubtype HIV-1 genetic variability, it has been shown that subtype-specific patterns of resistance to antiretroviral drugs exist. We wished to ascertain whether this might be true for integrase inhibitors.
We compared the susceptibility of subtype B and C HIV-1 integrase enzymes, harboring the previously reported resistance mutations E92Q, N155H, and E92Q/N155H, to clinically relevant integrase inhibitors. This was performed biochemically using a microtiter plate system.
Subtype C integrase enzymes bearing the resistance mutations E92Q/N155H were approximately 10-fold more susceptible to each of two integrase inhibitors, raltegravir and elvitegravir, than were subtype B recombinant integrase containing the same mutations.
Polymorphic differences within the subtype B and C integrase genes likely cause variations in the contribution of N155H alone or in combination with E92Q to drug resistance. It is possible that different viral subtypes may favor different mutational pathways, potentially leading to varying levels of drug resistance among different subtypes.
由于 HIV-1 亚型间存在高度的遗传变异性，已经表明存在针对抗逆转录病毒药物的亚型特异性耐药模式。我们希望确定这是否适用于整合酶抑制剂。
我们比较了携带先前报道的耐药突变 E92Q、N155H 和 E92Q/N155H 的 B 型和 C 型 HIV-1 整合酶酶对临床相关整合酶抑制剂的敏感性。这是通过使用微量滴定板系统进行的生化分析来完成的。
与含有相同突变的 B 型重组整合酶相比，携带耐药突变 E92Q/N155H 的 C 型整合酶对两种整合酶抑制剂raltegravir 和 elvitegravir 的敏感性约高 10 倍。
B 型和 C 型整合酶基因内的多态性差异可能导致 N155H 单独或与 E92Q 联合对药物耐药性的贡献发生变化。不同的病毒亚型可能有利于不同的突变途径，从而导致不同亚型之间的药物耐药性水平存在差异。
Zotero 插件