Garrido Carolina, de Mendoza Carmen, Soriano Vicente
Servicio de Enfermedades Infecciosas, Hospital Carlos III, Madrid, España.
Enferm Infecc Microbiol Clin. 2008 Nov;26 Suppl 12:40-6. doi: 10.1016/s0213-005x(08)76572-8.
Integrase inhibitors are the most recently approved family of antiretroviral agents for the treatment of HIV infection. As with other antiretroviral agents, under pharmacological pressure, the virus selects resistance mutations if viral suppression is incomplete. Mutations are selected in the integrase gene, specifically in positions proximal to the catalytic center. Because clinical experience with these drugs is scarce, information on resistance is limited. Virologic failure with raltegravir is associated with selection of primary mutations such as N155H (40%) and distinct changes in position Q148 (28%). Less frequently, Y143R (6.6%) and E92Q are selected. The most frequently observed mutations in failure with elvitegravir are E92Q, E138K, Q148R/K/H and N155H, and less frequently S147G and T66A/I/K. The most common resistance pattern seems to be E138K + E147G + Q148R. There is a high grade of cross resistance between raltegravir and elvitegravir, making sequencing between these two drugs impossible.
整合酶抑制剂是最近被批准用于治疗HIV感染的一类抗逆转录病毒药物。与其他抗逆转录病毒药物一样,在药理压力下,如果病毒抑制不完全,病毒会选择耐药突变。突变发生在整合酶基因中,特别是在催化中心附近的位置。由于这些药物的临床经验较少,关于耐药性的信息有限。raltegravir治疗失败与主要突变的选择有关,如N155H(40%)和Q148位置的明显变化(28%)。较少见的是Y143R(6.6%)和E92Q。elvitegravir治疗失败时最常观察到的突变是E92Q、E138K、Q148R/K/H和N155H,较少见的是S147G和T66A/I/K。最常见的耐药模式似乎是E138K + E147G + Q148R。raltegravir和elvitegravir之间存在高度交叉耐药性,使得这两种药物之间无法进行测序。