Avi Radko, Huik Kristi, Sadam Maarja, Karki Tonis, Krispin Tonu, Ainsalu Külliki, Paap Piret, Schmidt Jelena, Nikitina Natalia, Lutsar Irja
Faculty of Medicine, Department of Microbiology, University of Tartu, Tartu, Estonia.
J Med Virol. 2009 Jun;81(6):953-8. doi: 10.1002/jmv.21482.
All non-B HIV-1 subtypes and circulating recombinant forms (CRFs) are characterized by several polymorphisms in protease (PR) region. In addition, in recent years the increasing use of antiretroviral treatment (ART) has rapidly raised the spread of transmitted drug resistance. We aimed to determine the presence of naturally occurring polymorphisms and transmitted drug resistance mutations (DRMs) in ART naïve HIV-1-positive subjects in Estonia. A total of 115 drug-naive HIV-1-infected subjects (mean age 27 years; 70% male; 65% infected via intravenous drug use and 34% by heterosexual contact) were enrolled. Viral genomic RNA from plasma was directly sequenced in PR, revertase (RT), and envelope (env) regions. Phylogenetic analysis of RT and env regions revealed that 89% and 3% of sequenced viruses belonged to CRF06_cpx and subtype A1, respectively, and 6% were described as unique recombinants (signed A1-06) between CRF06_cpx and subtype A1 viruses. No primary DRMs were found in PR or RT regions indicating the absence of transmitted drug resistance. The most common polymorphisms in the PR region were K14R, M36I, H69K, and L89M seen in 96%, 100%, 99%, and 100%, respectively. The clinical relevance of these polymorphisms in terms of success of ART has to be monitored in future clinical studies.
所有非B型HIV-1亚型和循环重组型(CRF)在蛋白酶(PR)区域都有几种多态性特征。此外,近年来抗逆转录病毒治疗(ART)的使用增加迅速提高了传播性耐药的传播率。我们旨在确定爱沙尼亚未接受过ART治疗的HIV-1阳性受试者中自然发生的多态性和传播性耐药突变(DRM)的存在情况。共纳入了115名未接受过药物治疗的HIV-1感染受试者(平均年龄27岁;70%为男性;65%通过静脉吸毒感染,34%通过异性接触感染)。对血浆中的病毒基因组RNA在PR、逆转录酶(RT)和包膜(env)区域进行直接测序。RT和env区域的系统发育分析显示,分别有89%和3%的测序病毒属于CRF06_cpx和A1亚型,6%被描述为CRF06_cpx和A1亚型病毒之间的独特重组体(标记为A1-06)。在PR或RT区域未发现原发性DRM,表明不存在传播性耐药。PR区域最常见的多态性分别为K14R、M36I、H69K和L89M,出现频率分别为96%、100%、99%和100%。这些多态性在ART治疗成功方面的临床相关性有待未来临床研究监测。