Delaugerre C
Université Paris Diderot, Laboratoire de virologie, Hôpital Saint Louis, AP-HP, 1 avenue Claude Vellefaux, 75010 Paris, France.
Med Mal Infect. 2010 Sep;40 Suppl 1:S1-10. doi: 10.1016/S0399-077X(10)70001-9.
The genetic barrier for the antiretroviral describes the ability to select resistant viruses to this antiretroviral when the viral replication is not controlled. This includes combining several concepts: (1) the number of nucleotide changes required for a resistance mutation, (2) the impact of this mutation on the level of susceptibility to antiretroviral (3) the impact of this mutation on viral replication capacity; all theses conditions influencing the level of resistant variants. The antiretroviral concentration impact also the emergence of resistance. Finally, combine with other molecules, the selection of resistance mutations ton an antiretroviral may differ from one treatment to another. It is recognized that the genetic barrier to lamivudine/emtricitabine, efavirenz and nevirapine is low, and is intermediate for nucleoside such as zidovudine and tenofovir. However, ritonavir boosted protease inhibitor with high plasma concentration have a high genetic barrier. For integrase inhibitors such as raltegravir, the emergence of resistance is certainly faster than the ritonavir boosted protease inhibitors, but seems slower and less systematic than for efavirenz or lamivudine. Many factors could influence the raltegravir resistance such as the level of viral load and replication duration, genetic polymorphism of HIV (integrase gene and other, viral subtype) and the plasma and/or intra- cellular raltegravir concentration.
抗逆转录病毒药物的基因屏障描述了在病毒复制未得到控制时选择对该抗逆转录病毒药物耐药的病毒的能力。这包括几个概念：（1）耐药突变所需的核苷酸变化数量；（2）该突变对抗逆转录病毒药物敏感性水平的影响；（3）该突变对病毒复制能力的影响；所有这些条件都会影响耐药变异体的水平。抗逆转录病毒药物的浓度也会影响耐药性的出现。最后，与其他分子联合使用时，抗逆转录病毒药物耐药突变的选择可能因治疗方案而异。人们认识到，拉米夫定/恩曲他滨、依非韦伦和奈韦拉平的基因屏障较低，而齐多夫定和替诺福韦等核苷类药物的基因屏障处于中等水平。然而，血浆浓度高的利托那韦增强型蛋白酶抑制剂具有较高的基因屏障。对于雷特格韦等整合酶抑制剂，耐药性的出现肯定比利托那韦增强型蛋白酶抑制剂更快，但似乎比利匹韦林或拉米夫定更慢且更不具有系统性。许多因素可能影响雷特格韦耐药性，如病毒载量水平和复制持续时间、HIV的基因多态性（整合酶基因及其他、病毒亚型）以及血浆和/或细胞内雷特格韦浓度。
