Mendoza Carmen De, Garrido Carolina, Treviño Ana, Anta Lourdes, Poveda Eva, Soriano Vicente
Servicio de Enfermedades Infecciosas, Hospital Carlos III, Madrid, España.
Enferm Infecc Microbiol Clin. 2008 Dec;26 Suppl 17:28-33. doi: 10.1016/S0213-005X(08)76617-5.
Resistance to protease inhibitors (PI) is generally due to a mutation in the protease gene. Different changes have been described for each PI. The I 50L mutation is characteristic of resistance to atazanavir (ATV). It does not produce cross resistance to other PI; but it does increase susceptibility to all of them (hypersusceptibility). When PI are given concomitantly with low doses of ritonavir, the exposure to higher levels of PI requires that multiple resistance mutations have to be selected in the protease so that there is a significant loss of susceptibility. For the majority of PI/r, including ATV/r, >or=5 mutations in the protease are required to produce a compromise in the virological response. Despite having a moderate genetic barrier when not boosted with ritonavir, the prolonged half life of ATV minimises the risk of resistance in clinical practice.
对蛋白酶抑制剂（PI）的耐药性通常是由于蛋白酶基因发生突变。针对每种PI都描述了不同的变化。I50L突变是对阿扎那韦（ATV）耐药的特征性突变。它不会对其他PI产生交叉耐药性；但它确实会增加对所有PI的敏感性（超敏感性）。当PI与低剂量利托那韦同时给药时，要接触更高水平的PI就需要在蛋白酶中选择多个耐药突变，从而导致敏感性显著丧失。对于大多数PI/r，包括ATV/r，蛋白酶中需要有≥5个突变才能在病毒学应答中产生折衷。尽管在未用利托那韦增强时具有中等的遗传屏障，但ATV延长的半衰期在临床实践中使耐药风险降至最低。
