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导致西西里岛血清阳性者对抗逆转录病毒药物产生耐药性的HIV基因组突变。

HIV genomic mutations causing resistance to antiretroviral drugs in seropositive Sicilians.

作者信息

Bertuccio Maria Paola, Picerno Isa, Celesia Benedetto Maurizio, Galvagna Salvatore, Sturniolo Giuseppe, Spataro Pasquale, Visalli Giuseppa

机构信息

Via Consolare Valeria, Messina, Italy.

出版信息

Curr HIV Res. 2014;12(1):32-43. doi: 10.2174/1570162x12666140512112112.

Abstract

Through the use of highly active antiretroviral therapy a significant reduction occurred in mortality and morbidity caused by Human Immunodeficiency Virus. The use of antiretroviral drugs resulted in the emergence of resistant viral strains due to mutations that cause a selective advantage to the virus. The aim of our study is to monitor the HIV-1 infection in Sicilians patients evaluating the presence of mutations that make the virus resistant to the therapy. The QIAGEN QIAamp Viral RNA Mini Kit was used to extract HIV-1 viral RNA from 300 patients while the TRUGENE HIV-1 Genotyping Kit and the OpenGene DNA Sequencing System determined viral mutations in the RNA samples. The analysis showed that from 300 subjects, 116 developed Antiretroviral Drug Resistance. The percentage of patients with resistance to nucleoside reverse transcriptase inhibitor (NRTI), non nucleoside reverse transcriptase inhibitor (NNRTI) and protease inhibitor was 26%, 23% and 20%, respectively. Comparison between drug resistances and mutations showed that 134 individuals had mutations in genes codifying for reverse transcriptase but a little more than 50% were associated with resistance to reverse transcriptase inhibitors, in particular 78 and 68 subjects developed drug resistances to NRTI and NNRTI classes respectively. Subjects that showed mutations in genes codifying for protease were 216 but only 59 of these were associated with resistance to protease inhibitors. Our findings emphasize the importance of continued resistance surveillance. Monitoring of transmitted resistance continues to be needed among treatment-exposed patients because of the benefit it provides for the development of drugs effective against the most frequently found drug-resistant viruses.

摘要

通过使用高效抗逆转录病毒疗法,人类免疫缺陷病毒所致的死亡率和发病率显著降低。抗逆转录病毒药物的使用导致了耐药病毒株的出现,这是由赋予病毒选择性优势的突变引起的。我们研究的目的是监测西西里岛患者的HIV-1感染情况,评估使病毒对治疗产生耐药性的突变的存在情况。使用QIAGEN QIAamp病毒RNA迷你试剂盒从300名患者中提取HIV-1病毒RNA,同时使用TRUGENE HIV-1基因分型试剂盒和OpenGene DNA测序系统确定RNA样本中的病毒突变。分析表明,在300名受试者中,有116人产生了抗逆转录病毒药物耐药性。对核苷类逆转录酶抑制剂(NRTI)、非核苷类逆转录酶抑制剂(NNRTI)和蛋白酶抑制剂耐药的患者百分比分别为26%、23%和20%。药物耐药性与突变之间的比较表明,134人在编码逆转录酶的基因中有突变,但其中略多于50%与对逆转录酶抑制剂的耐药性有关,特别是分别有78名和68名受试者对NRTI类和NNRTI类药物产生了耐药性。在编码蛋白酶的基因中显示有突变的受试者有216人,但其中只有59人与对蛋白酶抑制剂的耐药性有关。我们的研究结果强调了持续进行耐药性监测的重要性。由于其对开发针对最常见耐药病毒的有效药物具有益处,因此在接受治疗接触的患者中仍需要监测传播性耐药性。

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