Shafer Robert W, Kantor Rami, Gonzales Matthew J
Division of Infectious Diseases and Geographic Medicine, Stanford University, Stanford, CA, USA.
AIDS Rev. 2000;2(4):211-228.
HIV-1 drug resistance is caused by mutations in the reverse transcriptase (RT) and protease enzymes, the molecular targets of antiretroviral therapy. At the beginning of the year 2000, two expert panels recommended that HIV-1 RT and protease susceptibility testing be used to help select antiretroviral drugs for HIV-1-infected patients. Genotypic assays have been developed to detect HIV-1 mutations known to confer antiretroviral drug resistance. Genotypic assays using dideoxynucleoside sequencing provide extensive insight into the presence of drug-resistant variants in the population of viruses within an individual. However, the interpretation of these assays in clinical settings is formidable because of the large numbers of drug resistance mutations and because these mutations interact with one another and emerge in complex patterns. In addition, cross-resistance between antiretroviral drugs is greater than that anticipated from initial in vitro studies. This review summarises the published data linking HIV-1 RT and protease mutations to in vitro and clinical resistance to the currently available nucleoside RT inhibitors, non-nucleoside RT inhibitors, and protease inhibitors.
HIV-1耐药性是由逆转录酶（RT）和蛋白酶的突变引起的，这两种酶是抗逆转录病毒疗法的分子靶点。2000年初，两个专家小组建议使用HIV-1 RT和蛋白酶敏感性检测来帮助为感染HIV-1的患者选择抗逆转录病毒药物。已经开发出基因分型检测方法来检测已知会导致抗逆转录病毒药物耐药性的HIV-1突变。使用双脱氧核苷测序的基因分型检测方法能够深入了解个体体内病毒群体中耐药变异体的存在情况。然而，由于耐药突变数量众多，且这些突变相互作用并以复杂的模式出现，在临床环境中对这些检测结果的解读颇具难度。此外，抗逆转录病毒药物之间的交叉耐药性比最初的体外研究所预期的要大。本综述总结了已发表的数据，这些数据将HIV-1 RT和蛋白酶突变与目前可用的核苷类逆转录酶抑制剂、非核苷类逆转录酶抑制剂和蛋白酶抑制剂的体外及临床耐药性联系起来。
