Antoniadou Zoi-Anna, Hezka Johana, Kousiappa Ioanna, Mamais Ioannis, Skoura Lemonia, Pilalas Dimitris, Metallidis Simeon, Nicolaidis Pavlos, Malisiovas Nicolaos, Kostrikis Leondios G
1 AIDS National Reference Laboratory of Northern Greece, Department of Microbiology, School of Medicine, Aristotle University of Thessaloniki , Thessaloniki, Greece .
AIDS Res Hum Retroviruses. 2014 Mar;30(3):266-71. doi: 10.1089/AID.2013.0160. Epub 2013 Oct 9.
The emergence of resistance against current antiretroviral drugs to human immunodeficiency virus type 1 (HIV-1) is an increasingly important concern to the continuous success of antiretroviral therapy to HIV-1-infected patients. In the past decade, a number of studies reported that the prevalence of transmitted drug resistance among newly diagnosed patients has reached an overall 9% prevalence worldwide. Also, a number of studies using longitudinal HIV-1 patient study cohorts demonstrated that the cellular HIV-1 DNA level in peripheral blood mononuclear cells (PBMCs) has a prognostic value for the progression of HIV-1 disease independently of plasma HIV-1 RNA load and CD4 count. Using a previously established molecular-beacon-based real-time PCR methodology, cellular HIV-1 DNA levels were quantified in newly diagnosed and antiretroviral-naive patients in Northern Greece recruited between 2009 and 2010 using a predefined enrolling strategy, in an effort to investigate whether there is any relationship between cellular HIV-1 DNA levels and HIV-1 transmitted drug resistance. As part of the same study, DNA sequences encoding the env (C2-C5 region of gp120) were also amplified from PBMC-extracted DNA in order to determine the genotypic coreceptor tropism and genetic subtype. Cellular HIV-1 DNA levels had a median of 3.309 log10 HIV-1 copies per 10(6) PBMCs and demonstrated no correlation between cellular HIV-1 DNA levels and HIV-1 transmitted drug resistance. An absence of association between cellular HIV-1 DNA levels with plasma viral HIV-1 RNA load and CD4 levels was also found reconfirming the previously published study. Genotypic analysis of coreceptor tropism indicated that 96% of samples, independently of the presence or not of genotypic drug resistance, were CCR5-tropic. Overall, the findings reconfirmed the previously proposed proposition that transmitted drug resistance does not have an impact on disease progression in HIV-1-infected individuals. Also, CCR5 coreceptor tropism dominance suggests that both drug-resistant and drug-sensitive strains behave similarly in early infection in newly diagnosed patients.
对人类免疫缺陷病毒1型(HIV-1)而言,目前抗逆转录病毒药物出现耐药性,这对于抗逆转录病毒疗法在HIV-1感染患者中的持续成功治疗而言,是一个日益重要的问题。在过去十年中,多项研究报告称,新诊断患者中传播性耐药的总体患病率在全球范围内已达到9%。此外,一些使用HIV-1患者纵向研究队列的研究表明,外周血单个核细胞(PBMC)中的细胞HIV-1 DNA水平对HIV-1疾病进展具有预后价值,独立于血浆HIV-1 RNA载量和CD4计数。使用先前建立的基于分子信标的实时PCR方法,在2009年至2010年期间,采用预定义的招募策略,对希腊北部新诊断且未接受过抗逆转录病毒治疗的患者的细胞HIV-1 DNA水平进行了定量,以研究细胞HIV-1 DNA水平与HIV-1传播性耐药之间是否存在任何关系。作为同一研究的一部分,还从PBMC提取的DNA中扩增了编码env(gp120的C2-C5区域)的DNA序列,以确定基因型共受体嗜性和基因亚型。细胞HIV-1 DNA水平的中位数为每10(6)个PBMC中有3.309 log10 HIV-1拷贝,且细胞HIV-1 DNA水平与HIV-1传播性耐药之间无相关性。还发现细胞HIV-1 DNA水平与血浆病毒HIV-1 RNA载量和CD4水平之间不存在关联,再次证实了先前发表的研究。共受体嗜性的基因型分析表明,96%的样本,无论是否存在基因型耐药,均为CCR5嗜性。总体而言,这些发现再次证实了先前提出的观点,即传播性耐药对HIV-1感染个体的疾病进展没有影响。此外,CCR5共受体嗜性占主导地位表明,耐药和药物敏感菌株在新诊断患者的早期感染中表现相似。