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Drug resistance-associated mutations in antiretroviral treatment-naive and -experienced patients in Kuwait

机译:抗逆转录病毒治疗 - 天真且 - 科威特患者的耐药相关突变

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The identification of human immunodeficiency virus (HIV) mutations leading to drug resistance enables patient-specific adaptation of the treatment regimen and predicts the risk of transmission of drug-resistant HIV. In this study, we report for the first time the prevalence in Kuwait of non-polymorphic resistance-associated mutations (RAMs) in patients under first-line antiretroviral therapy. Viral RNA was extracted from plasma samples of 64 treatment-naive (untreated) and 64 treatment-experienced patients. The HIV-1 load was determined by real-time RT-PCR. The protease- and reverse transcriptase-encoding regions were analyzed by subtyping, and for drug resistance. The HIV-1 load at sampling in treatment-naive patients ranged from 1.61 x 10(4) to 1.91 x 10(6) copies/ml, whereas that in treatment-experienced patients ranged from 20 to 8.25 x 10(4) copies/ml (p 0.001). Ten different HIV-1 subtypes and recombinant forms were found with the predominance of CRF01_AE, B and C. Non-polymorphic mutations associated with resistance to antiretroviral drugs were detected in 8 treatment-naive patients (12.5%) and 11 treatment-experienced patients (28.9%; p = 0.46). RAMS detected in treatment-naive patients are known to be associated with resistance to non-nucleoside reverse transcriptase inhibitors (NNRTIs). Among treatment-experienced patients, five patients (13.1%) had mutations associated with high-level resistance to nucleoside reverse transcriptase inhibitors (NRTIs), 4 patients (10.5%) had mutations associated with resistance to NNRTIs, one patient (2.6%) had resistance to both NRTIs and NNRTIs, and one patient (2.6%) had resistance to both protease inhibitors (Pis) and NNRTIs. These results necessitate efforts to be made for reducing emergence of resistance-associated mutations in treated patients, and highlight the need for continuous monitoring of drug resistance patterns in Kuwait.
机译:导致耐药性的人免疫缺陷病毒(HIV)突变的鉴定使得能够特异性适应治疗方案,并预测耐药艾滋病毒的传播风险。在这项研究中,我们首次报告了一线抗逆转录病毒治疗患者的非多态性抗性相关突变(RAMS)的第一次患病率。从64个处理 - 幼稚(未处理)和64名治疗患者的血浆样品中提取病毒RNA。通过实时RT-PCR测定HIV-1负荷。通过亚型分析蛋白酶和逆转录酶编码区域,并进行耐药性。治疗野患者的取样时的HIV-1负载范围为1.61×10(4)至1.91×10(6)份/ mL,而在治疗中,在治疗中的患者范围为20至8.25 x 10(4)拷贝/ ml(p <0.001)。发现了十种不同的HIV-1亚型和重组形式,具有CRF01_AE,B和C.在8例治疗危险患者(12.5%)和11名治疗患者( 28.9%; p = 0.46)。已知在治疗幼稚患者中检测到的RAMs与对非核苷逆转录酶抑制剂(NNRTIS)的抗性相关。在治疗经验丰富的患者中,五名患者(13.1%)具有与核苷逆转录酶抑制剂(NRTIS)的高水平抗性相关的突变,4名患者(10.5%)具有与NNRTIS抗性相关的突变,一名患者(2.6%)对NRTIS和NNRTIS的抵抗力,一名患者(2.6%)对蛋白酶抑制剂(PIS)和NNRTIS具有抗性。这些结果需要努力减少治疗患者中抗性相关突变的出现,并突出了对科威特耐药模式的不断监测。

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