Distribution of hepatitis С virus drug resistance mutations among patients with recurrence of the disease during therapy with direct antiviral drugs

D. E. Reingardt, Y. Ostankova, L. V. Lyalina, E. V. Anufrieva, A. V. Semenov, A. A. Totolian
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Abstract

The aim of the study was to identify the prevalence of drug resistance mutations in the hepatitis C virus among patients with relapse of the disease on therapy with direct antiviral drugs.Materials and methods. The study material included 31 blood plasma samples from patients with chronic hepatitis C with relapse of the disease on therapy with direct antiviral drugs. Samples were screened for the presence of HCV RNA. In case of detection of HCV RNA, amplification was carried out using a set of primers jointly flanking the NS3, NS5A, NS5B genes. After sequencing the nucleotide sequences of these genes, the subtype of the virus was determined and drug resistance mutations were identified.Results and discussion. The age of the patients ranged from 33 to 62 and averaged 45.8±8.38 years. The number of men in the group prevailed compared to women — 21 (67%) and 10 (33%), respectively. Viral load determination results ranged from 3.1×103 to 4.2×107 IU/ml. The distribution of genotypes was as follows: 1a — 26% (n=8), 1b — 29% (n=9), 3a — 45% (n=14). The nucleotide sequence of the NS3, NS5A, NS5B regions was determined in all samples. Mutations associated with drug resistance were detected in 87% (n=27). In all identified cases, the mutations resulted in viral resistance to at least one drug included in the patient’s current treatment regimen. In one patient, amino acid substitutions were found in three regions at once, which led to the emergence of resistance to two drugs in the regimen.Conclusion. Conducting a preliminary examination of patients to identify mutations of drug resistance to direct antiviral drugs can affect the effectiveness of the planned treatment and the choice of the optimal regimen.
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直接抗病毒药物治疗期间病情复发患者中С型肝炎病毒耐药性变异的分布情况
该研究旨在确定直接抗病毒药物治疗后复发的丙型肝炎患者中丙型肝炎病毒耐药突变的流行情况。研究材料包括 31 份血浆样本,这些样本来自接受直接抗病毒药物治疗后复发的慢性丙型肝炎患者。对样本进行筛查,以确定是否存在 HCV RNA。在检测到 HCV RNA 的情况下,使用 NS3、NS5A 和 NS5B 基因侧翼的一组引物进行扩增。对这些基因的核苷酸序列进行测序后,确定了病毒的亚型,并确定了耐药性突变。患者年龄从 33 岁到 62 岁不等,平均年龄(45.8±8.38)岁。该组患者中男性多于女性,分别为 21 人(67%)和 10 人(33%)。病毒载量测定结果为 3.1×103 至 4.2×107 IU/ml。基因型分布如下1a - 26%(8 人),1b - 29%(9 人),3a - 45%(14 人)。所有样本的 NS3、NS5A、NS5B 区域的核苷酸序列均已测定。87%的样本(n=27)检测到了与耐药性相关的突变。在所有确定的病例中,突变导致病毒对患者当前治疗方案中的至少一种药物产生耐药性。在一名患者身上,同时在三个区域发现了氨基酸置换,导致对治疗方案中的两种药物产生耐药性。对患者进行初步检查以确定对直接抗病毒药物的耐药性变异,会影响计划治疗的效果和最佳治疗方案的选择。
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来源期刊
HIV Infection and Immunosuppressive Disorders
HIV Infection and Immunosuppressive Disorders Medicine-Infectious Diseases
CiteScore
0.70
自引率
0.00%
发文量
37
期刊介绍: In the scientific-practical journal "HIV Infection and Immunosuppressive Disorders", published various issues of HIV medicine (epidemiology, molecular mechanisms of pathogenesis to the development of educational programs) leading scientists of Russia and countries of CIS, USA, as well as practical healthcare professionals working in research centers, research institutes, universities, clinics where done basic medical work. A special place on the pages of the publication is given to basic and clinical research, analytical reviews of contemporary and foreign reports, the provision of medical care for various diseases.
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