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首页> 外文期刊>PLoS One >Cellular HIV-1 DNA Levels in Drug Sensitive Strains Are Equivalent to Those in Drug Resistant Strains in Newly-Diagnosed Patients in Europe
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Cellular HIV-1 DNA Levels in Drug Sensitive Strains Are Equivalent to Those in Drug Resistant Strains in Newly-Diagnosed Patients in Europe

机译：在欧洲，新发现的患者中药物敏感菌株的细胞HIV-1 DNA水平与耐药菌株相同

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Background HIV-1 genotypic drug resistance is an important threat to the success of antiretroviral therapy and transmitted resistance has reached 9% prevalence in Europe. Studies have demonstrated that HIV-1 DNA load in peripheral blood mononuclear cells (PBMC) have a predictive value for disease progression, independently of CD4 counts and plasma viral load. Methodology/Principal Findings Molecular-beacon-based real-time PCR was used to measure HIV-1 second template switch (STS) DNA in PBMC in newly-diagnosed HIV-1 patients across Europe. These patients were representative for the HIV-1 epidemic in the participating countries and were carrying either drug-resistant or sensitive viral strains. The assay design was improved from a previous version to specifically detect M-group HIV-1 and human CCR5 alleles. The findings resulted in a median of 3.32 log10 HIV-1 copies/106 PBMC and demonstrated for the first time no correlation between cellular HIV-1 DNA load and transmitted drug-resistance. A weak association between cellular HIV-1 DNA levels with plasma viral RNA load and CD4+ T-cell counts was also reconfirmed. Co-receptor tropism for 91% of samples, whether or not they conferred resistance, was CCR5. A comparison of pol sequences derived from RNA and DNA, resulted in a high similarity between the two. Conclusions/Significance An improved molecular-beacon-based real-time PCR assay is reported for the measurement of HIV-1 DNA in PBMC and has investigated the association between cellular HIV-1 DNA levels and transmitted resistance to antiretroviral therapy in newly-diagnosed patients from across Europe. The findings show no correlation between these two parameters, suggesting that transmitted resistance does not impact disease progression in HIV-1 infected individuals. The CCR5 co-receptor tropism predominance implies that both resistant and non-resistant strains behave similarly in early infection. Furthermore, a correlation found between RNA- and DNA-derived sequences in the pol region suggests that genotypic drug-resistance testing could be carried out on either template.
机译：背景技术HIV-1基因型耐药性是抗逆转录病毒疗法成功的重要威胁，在欧洲，传播的耐药性已达到9％的患病率。研究表明，外周血单核细胞（PBMC）中的HIV-1 DNA负荷对疾病进展具有预测价值，与CD4计数和血浆病毒负荷无关。方法/主要发现基于分子信标的实时PCR用于测量欧洲新诊断的HIV-1患者PBMC中的HIV-1第二模板转换（STS）DNA。这些患者代表了参与国的HIV-1流行病，并携带耐药性或敏感病毒株。该测定设计比以前的版本有所改进，可以特异性检测M组HIV-1和人类CCR5等位基因。该发现导致中位数为3.32 log10 HIV-1拷贝/ 106 PBMC，并首次证明细胞HIV-1 DNA载量与传播的耐药性之间无相关性。还证实了细胞HIV-1 DNA水平与血浆病毒RNA载量和CD4 + T细胞计数之间的弱关联。不论是否赋予抗药性，91％样品的共受体嗜性为CCR5。来自RNA和DNA的pol序列的比较导致两者之间的高度相似性。结论/意义据报道，一种改进的基于分子信标的实时PCR测定法可用于PBMC中HIV-1 DNA的测定，并研究了新诊断患者中细胞HIV-1 DNA水平与抗逆转录病毒疗法的传播耐药性之间的关系。来自整个欧洲研究结果表明这两个参数之间没有相关性，表明传播的耐药性不会影响HIV-1感染者的疾病进展。 CCR5共受体向性优势表明抗性和非抗性菌株在早期感染中的行为相似。此外，在pol区域的RNA和DNA衍生的序列之间发现相关性，这表明可以在任一模板上进行基因型耐药性测试。

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