Single- and multidrug resistance mutations to reverse transcriptase and protease inhibitors: human immunodeficiency virus type 1-infected patients from two geographical areas in Spain. Spanish Groups for Antiretroviral Resistance Studies.

Journal of human virology Pub Date : 2000-05-01
L Pérez-Alvarez, M L Villahermosa, M T Cuevas, E Delgado, N Manjón, E Vázquez de Parga, L Medrano, G Contreras, M M Thomson, C Colomo, J A Taboada, R Nájera
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Abstract

Objectives: To describe the prevalence of genotypic resistance mutations, including single and multidrug resistance (MDR) to reverse transcriptase (RT) and protease (PR) inhibitors in treated and untreated patients from two geographical areas in Spain (Madrid and Galicia).

Study design/methods: Resistance mutations to RT inhibitors were studied by line probe assay (LiPA) or by automated sequencing in 468 patients (Madrid, 268; Galicia, 200), and resistance mutations to PR inhibitors were studied by automated sequencing in 295 patients (Madrid, 85; Galicia, 210).

Results: The proportion of resistance mutations in treated and untreated patients results were higher by the LiPA method than by sequencing. By sequencing, we detected resistance mutations to nucleoside analogue RT (NRT) inhibitors and NRT inhibitors plus nonnucleoside RT (NNRT) inhibitors in 35.4% and 17.2% of treated patients, respectively. We also detected MDR to zidovudine plus lamivudine in 13.9% of treated patients from Galicia, in 1.7% from Madrid (p < 0.001), and in 1.5% of untreated patients from Galicia. Also, we detected MDR to NRT inhibitors in 3.8% and to NNRT inhibitors in 9.1%. We found resistance mutations to PR inhibitors in 38.1% of treated patients and in 0.9% of untreated patients.

Conclusions: These findings reinforce the usefulness of testing for resistance mutations in some cases to evaluate their prevalence in a given population and in the follow-up of treated patients.

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对逆转录酶和蛋白酶抑制剂的单药和多药耐药突变:来自西班牙两个地理区域的人类免疫缺陷病毒1型感染患者西班牙抗逆转录病毒耐药性研究小组。
目的:描述来自西班牙两个地理区域(马德里和加利西亚)的治疗和未治疗患者的基因型耐药突变的患病率,包括对逆转录酶(RT)和蛋白酶(PR)抑制剂的单药和多药耐药(MDR)。研究设计/方法:通过线探针测定(LiPA)或自动测序研究了468例患者对RT抑制剂的抗性突变(Madrid, 268;Galicia, 2000)和对PR抑制剂的耐药突变在295例患者中通过自动测序进行了研究(Madrid, 85;加利西亚,210)。结果:LiPA法在治疗组和未治疗组的耐药突变比例均高于测序法。通过测序,我们分别在35.4%和17.2%的治疗患者中检测到对核苷类似物RT (NRT)抑制剂和NRT抑制剂加非核苷RT (NNRT)抑制剂的耐药突变。我们还在加利西亚13.9%的治疗患者中检测到齐多夫定加拉米夫定的耐多药,在马德里为1.7% (p < 0.001),在加利西亚1.5%的未治疗患者中检测到耐多药。此外,我们检测到对NRT抑制剂的耐药率为3.8%,对NNRT抑制剂的耐药率为9.1%。我们发现38.1%的治疗患者和0.9%的未治疗患者对PR抑制剂有耐药性突变。结论:这些发现加强了在某些情况下检测耐药突变的有效性,以评估其在特定人群中的流行情况以及对治疗患者的随访。
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