Martínez G, Sarría L, Campelo C, Merchán A, Cisterna R
Departamento de Inmunología, Microbiología y Parasitología, Facultad de Medicina y Odontología de la Universidad del País Vasco, Bilbao.
Rev Esp Quimioter. 1999 Dec;12(4):317-24.
Genotypes that confer drug resistance to reverse transcriptase inhibitors and protease inhibitors were evaluated in HIV-1 proviral DNA obtained from peripheral blood mononuclear cell samples. Fifty-three HIV-1-infected patients were studied, 19 of whom had not received antiretroviral treatment. In the other 34 patients, 9 had been treated with combinations of two reverse transcriptase inhibitors (AZT, ddI, d4T, 3TC) and 25 had been treated with triple antiretroviral therapy including a protease inhibitor (nelfinavir, indinavir, saquinavir, ritonavir). To determine the presence of mutations involved in the development of resistance to reverse transcriptase inhibitors a hybridization Microtiter assay was carried out. Mutations were detected in treated patients as well as in those without previous antiretroviral treatment, with the most frequent mutations being those that confer resistance to AZT, followed by those that develop cross-resistance to ddI/ddC and 3TC, which are the most commonly used drugs to date. No mutations were detected to any nucleoside analog in only 13 cases. To analyze the presence of mutations in the protease gene a dot-blot hybridization was carried out which included the mutations in codons 36, 82 and 90. Mutation 82 was detected in one case. Therefore, with the aim of determining the pattern of genotypic mutations in patients infected with HIV-1 and in order to make the best therapeutic choice, it would be recommended to consider carrying out genotypic resistance assays in clinical practice.
在从外周血单个核细胞样本中获取的HIV-1前病毒DNA中,对赋予逆转录酶抑制剂和蛋白酶抑制剂耐药性的基因型进行了评估。研究了53例HIV-1感染患者,其中19例未接受过抗逆转录病毒治疗。在其他34例患者中,9例接受过两种逆转录酶抑制剂(齐多夫定、去羟肌苷、司他夫定、拉米夫定)联合治疗,25例接受过包括蛋白酶抑制剂(奈非那韦、茚地那韦、沙奎那韦、利托那韦)的三联抗逆转录病毒治疗。为了确定与逆转录酶抑制剂耐药性发展相关的突变的存在,进行了杂交微量滴定测定。在接受治疗的患者以及未接受过抗逆转录病毒治疗的患者中均检测到了突变,最常见的突变是赋予对齐多夫定耐药性的突变,其次是对去羟肌苷/双脱氧胞苷和拉米夫定产生交叉耐药性的突变,这两种是迄今为止最常用的药物。仅在13例中未检测到对任何核苷类似物的突变。为了分析蛋白酶基因中的突变存在情况,进行了斑点杂交,其中包括密码子36、82和90中的突变。在1例中检测到了82位点的突变。因此,为了确定HIV-1感染患者的基因型突变模式并做出最佳治疗选择,建议在临床实践中考虑进行基因型耐药性检测。