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HIV-1 逆转录酶和蛋白酶耐药突变检测在治疗经验和初治 HIV 感染者中的应用。

HIV-1 reverse transcriptase and protease mutations for drug-resistance detection among treatment-experienced and naïve HIV-infected individuals.

机构信息

Department of Virology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.

Research Center of Pediatric Infectious Diseases, Institute of Immunology and Infectious Diseases, Iran University of Medical Sciences, Tehran, Iran.

出版信息

PLoS One. 2020 Mar 2;15(3):e0229275. doi: 10.1371/journal.pone.0229275. eCollection 2020.

DOI:10.1371/journal.pone.0229275
PMID:32119691
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7051075/
Abstract

BACKGROUND

The presence of drug resistance mutations (DRMs) against antiretroviral agents is one of the main concerns in the clinical management of individuals with human immunodeficiency virus-1 (HIV-1) infection, especially in regions of the world where treatment options are limited. The current study aimed at assessing the prevalence of HIV-1 DRMs among naïve and treatment-experienced HIV-1-infected patients in Iran.

METHODS

From April 2013 to September 2018, the HIV-1 protease and reverse transcriptase genes were amplified and sequenced in plasma specimens of 60 newly diagnosed antiretroviral-naive individuals and 46 participants receiving antiretroviral therapies (ARTs) for at least six months with an HIV viral load of more than 1000 IU/mL to determine the HIV-1 DRMs and subtypes.

RESULTS

Among the 60 treatment-naïve HIV-1-infected participants, 8.3% were infected with HIV-1 variants with surveillance DRMs (SDRMs). The SDRMs, D67N and D67E, belonged to the NRTIs class in two patients and K103N and V106A belonged to the NNRTIs class in three patients. The phylogenetic analysis showed that 91.7% of the subjects were infected with subtype CRF35_AD, followed by subtype B (5.0%) and CRF01_AE (3.3%). Among the 46 ART-experienced participants, 33 (71.7%) carried HIV-1 variants with SDRMs (9.1% against PIs, 78.8% against NRTIs, and 100% against NNRTIs). M46I and I47V were the most common mutations for PIs, M184V was the most common mutation for the NRTIs, and K103N/S was the most common mutation for NNRTIs. Phylogenetic analysis of the polymerase region showed that all of the 46 HIV-1-infected patients who failed on ART carried CRF35_AD.

CONCLUSIONS

The moderate prevalence of SDRMs (8.3%) in treatment-naïve and ART-failed (77.1%) Iranian patients with HIV-1-infection emphasizes the need for systematic viral load monitoring, expanding drug resistance testing, carefully surveilling individuals on ART regimens, and facilitating access to new antiretrovirals by health authorities.

摘要

背景

抗逆转录病毒药物耐药突变(DRMs)的存在是人类免疫缺陷病毒-1(HIV-1)感染个体临床管理的主要关注点之一,尤其是在世界上治疗选择有限的地区。本研究旨在评估伊朗初治和经治 HIV-1 感染患者中 HIV-1 DRMs 的流行率。

方法

2013 年 4 月至 2018 年 9 月,对 60 例新诊断的抗逆转录病毒初治个体和 46 例接受抗逆转录病毒治疗(ART)至少 6 个月且 HIV 病毒载量>1000 IU/mL 的患者的血浆标本进行 HIV-1 蛋白酶和逆转录酶基因扩增和测序,以确定 HIV-1 DRMs 和亚型。

结果

在 60 例初治 HIV-1 感染患者中,8.3%的患者感染了具有监测耐药突变(SDRMs)的 HIV-1 变异株。SDRMs,D67N 和 D67E,存在于两名患者的 NRTIs 类药物中,而 K103N 和 V106A 存在于三名患者的 NNRTIs 类药物中。系统进化分析显示,91.7%的受试者感染了 CRF35_AD 亚型,其次是 B 亚型(5.0%)和 CRF01_AE 亚型(3.3%)。在 46 例接受 ART 的患者中,33 例(71.7%)携带具有 SDRMs 的 HIV-1 变异株(9.1%针对 PIs,78.8%针对 NRTIs,100%针对 NNRTIs)。M46I 和 I47V 是 PIs 最常见的突变,M184V 是 NRTIs 最常见的突变,而 K103N/S 是 NNRTIs 最常见的突变。聚合酶区的系统进化分析显示,所有在 ART 中失败的 46 例 HIV-1 感染患者均携带 CRF35_AD。

结论

在伊朗初治和 ART 失败(77.1%)的 HIV-1 感染患者中,SDRMs 的中等流行率(8.3%)强调了需要系统地监测病毒载量、扩大耐药性检测、仔细监测接受 ART 方案的个体,并为卫生当局提供新的抗逆转录病毒药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4403/7051075/21695de373d2/pone.0229275.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4403/7051075/b3d612980944/pone.0229275.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4403/7051075/21695de373d2/pone.0229275.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4403/7051075/b3d612980944/pone.0229275.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4403/7051075/21695de373d2/pone.0229275.g002.jpg

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