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初治失败的艾滋病患者中 HIV-1 耐药突变的发生率和类型。

Incidence and types of HIV-1 drug resistance mutation among patients failing first-line antiretroviral therapy.

机构信息

The 4th People's Hospital of Nanning, The Infectious Disease Hospital of Nanning Affiliated to Guangxi Medical University, and the AIDS Clinical Treatment Center of Guangxi (Nanning), Nanning, 530023, China.

The 4th People's Hospital of Nanning, The Infectious Disease Hospital of Nanning Affiliated to Guangxi Medical University, and the AIDS Clinical Treatment Center of Guangxi (Nanning), Nanning, 530023, China.

出版信息

J Pharmacol Sci. 2019 Apr;139(4):275-279. doi: 10.1016/j.jphs.2018.11.016. Epub 2019 Jan 17.

DOI:10.1016/j.jphs.2018.11.016
PMID:30928089
Abstract

OBJECTIVE

This study aims to investigate the prevalence and types of drug resistance mutations among patients failing first-line antiretroviral therapy (ART).

METHODS

Plasma samples from 112 patients with human immunodeficiency virus-1 (HIV-1) were collected for virus RNA extract and gene amplification. The mutations related to drug resistance were detected and the incidence was statistically analyzed, and the drug resistance rate against common drugs was also evaluated.

RESULTS

103 cases were successfully amplified, and the main drug resistance mutations in the reverse transcriptase (RT) region were M184V (50.49%), K103N (28.16%), Y181C (25.24%), and K65R (27.18%), while no drug main resistance mutation was found in the protease (PR) region. The incidence of drug resistance mutations was significantly different among patients with different ages, routes of infection, duration of treatment, initial ART regimens and viral load. The drug resistance rate to the common drugs was assessed, including Efavirenz (EFV, 71.84%), Nevirapine (NVP, 74.76%), Lamivudine (3TC, 66.02%), Zidovudine (AZT, 4.85%), Stavudine (D4T, 16.51%), and Tenofovir (TDF, 21.36%).

CONCLUSION

The drug resistance mutations to NRTIs and NNRTIs are complex and highly prevalent, which was the leading cause of first-line ART failure. This study provides significant theoretical support for developing the second-line and third-line therapeutic schemes.

摘要

目的

本研究旨在调查一线抗逆转录病毒治疗(ART)失败患者中耐药突变的流行率和类型。

方法

收集 112 例人类免疫缺陷病毒 1 型(HIV-1)患者的血浆样本进行病毒 RNA 提取和基因扩增。检测耐药相关突变并进行统计学分析,评估常见药物的耐药率。

结果

成功扩增 103 例,逆转录酶(RT)区主要耐药突变为 M184V(50.49%)、K103N(28.16%)、Y181C(25.24%)和 K65R(27.18%),而蛋白酶(PR)区未发现主要耐药突变。不同年龄、感染途径、治疗时间、初始 ART 方案和病毒载量患者的耐药突变发生率差异有统计学意义。评估了常见药物的耐药率,包括依非韦伦(EFV,71.84%)、奈韦拉平(NVP,74.76%)、拉米夫定(3TC,66.02%)、齐多夫定(AZT,4.85%)、司他夫定(D4T,16.51%)和替诺福韦(TDF,21.36%)。

结论

NRTIs 和 NNRTIs 的耐药突变复杂且高发,是一线 ART 失败的主要原因。本研究为制定二线和三线治疗方案提供了重要的理论支持。

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