Vázquez de Parga E, Rakhmanova A, Pérez-Alvarez L, Vinogradova A, Delgado E, Thomson M M, Casado G, Sierra M, Muñoz M, Carmona R, Vega Y, Contreras G, Medrano L, Osmanov S, Nájera R
Instituto de Salud Carlos III, Madrid, Spain.
J Med Virol. 2005 Nov;77(3):337-44. doi: 10.1002/jmv.20461.
There are few data on drug resistance-associated mutations in the former Soviet Union since, studies have usually been focused on the env or gag genes for subtype information. This study examines the prevalence and patterns of resistance-associated mutations to reverse transcriptase and protease inhibitors (RTI, PRI) in 278 HIV-1-infected treatment-naïve subjects from countries of Eastern Europe, and defines characteristic polymorphisms of RT and PR sequences in HIV-1 subtype A viruses. Blood samples were collected between 1997 and 2004. Plasma RNA was used for PR-RT amplification by reverse transcription coupled with nested PCR and sequencing. Phylogenetic analysis was done with neighbor-joining trees and bootscanning. Analysis of drug resistance mutations, with Stanford University HIV Drug Resistance Database's algorithm, resulted in an overall prevalence of 12.9% resistance to RTI and 3.9% to PRI. The most frequent substitutions in the RT region were at positions 62 and 236. V77I substitution in PR was found in 47.8% of samples. Polymorphisms in subtype A sequences were identified. This is the first study reporting the prevalence and patterns of both PRI and RTI resistance-associated mutations in naïve HIV-1 infected patients from the former Soviet Union. These data underline the importance of genotypic resistance testing of chronically HIV-1-infected patients before initiating treatment, in order to select the most suitable drug regimen.
在前苏联,关于耐药相关突变的数据很少,因为研究通常集中在env或gag基因以获取亚型信息。本研究调查了来自东欧国家的278例未经治疗的HIV-1感染受试者中对逆转录酶和蛋白酶抑制剂(RTI,PRI)的耐药相关突变的流行情况和模式,并确定了HIV-1 A亚型病毒中RT和PR序列的特征性多态性。于1997年至2004年期间采集血样。血浆RNA通过逆转录结合巢式PCR和测序用于PR-RT扩增。采用邻接法树和靴带扫描进行系统发育分析。使用斯坦福大学HIV耐药数据库的算法分析耐药突变,结果显示对RTI的总体耐药率为12.9%,对PRI的耐药率为3.9%。RT区域最常见的替换发生在第62和236位。在47.8%的样本中发现PR基因的V77I替换。鉴定出了A亚型序列中的多态性。这是第一项报告前苏联未经治疗的HIV-1感染患者中PRI和RTI耐药相关突变的流行情况和模式的研究。这些数据强调了在开始治疗前对慢性HIV-1感染患者进行基因型耐药检测的重要性,以便选择最合适的药物治疗方案。