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刚果共和国接受抗逆转录病毒治疗的患者中整合酶编码区无耐药突变

Absence of Resistance Mutations in the Integrase Coding Region among ART-Experienced Patients in the Republic of the Congo.

作者信息

Got Ferdinand Emaniel Brel, Recordon-Pinson Patricia, Loubano-Voumbi Ghislain, Ebourombi Dagene, Blondot Marie-Lise, Metifiot Mathieu, Ondzotto Gontran, Andreola Marie-Line

机构信息

Faculté des Sciences de la Santé, Université Marien Ngouabi, Brazzaville BP69, Democratic Republic of the Congo.

UMR 5234 Microbiologie Fondamentale et Pathogénicité, CNRS, Univ. Bordeaux, F-33000 Bordeaux, France.

出版信息

Microorganisms. 2021 Nov 15;9(11):2355. doi: 10.3390/microorganisms9112355.

Abstract

BACKGROUND

HIV infects around one hundred thousand patients in the Republic of the Congo. Approximately 25% of them receive an antiretroviral treatment; current first-line regimens include two NRTIs and one NNRTI, reverse transcriptase inhibitors. Recently, protease inhibitors (PIs) were also introduced as second-line therapy upon clinical signs of treatment failure. Due to the limited number of molecular characterizations and amount of drug resistance data available in the Republic of the Congo, this study aims to evaluate the prevalence of circulating resistance mutations within the region.

METHODS

HIV-positive, ART-experienced patients have been enrolled in four semi-urban localities in the Republic of the Congo. Plasma samples were collected, and viral RNA was extracted. The viral load for each patient was evaluated by RT-qPCR, following the general diagnostic procedures of the University Hospital of Bordeaux. Finally, drug resistance genotyping and phylogenetic analysis were conducted following Sanger sequencing of the region.

RESULTS

A high diversity of HIV-1 strains was observed with many recombinant forms. Drug resistance mutations in RT and PR genes were determined and correlated to HAART. Because integrase inhibitors are rarely included in treatments in the Republic of the Congo, the prevalence of integrase drug resistance mutations before treatment was also determined. Interestingly, very few mutations were observed.

CONCLUSIONS

We confirmed a high diversity of HIV-1 in the Republic of the Congo. Most patients presented an accumulation of mutations conferring resistance against NRTIs, NNRTIs and PIs. Nonetheless, the absence of integrase mutations associated with drug resistance suggests that the introduction of integrase inhibitors into therapy will be highly beneficial to patients in the Republic of the Congo.

摘要

背景

在刚果共和国,约有10万名患者感染了艾滋病毒。其中约25%的患者接受抗逆转录病毒治疗;目前的一线治疗方案包括两种核苷类逆转录酶抑制剂(NRTIs)和一种非核苷类逆转录酶抑制剂(NNRTIs),即逆转录酶抑制剂。最近,蛋白酶抑制剂(PIs)也被引入作为治疗失败临床症状出现后的二线治疗药物。由于刚果共和国可用的分子特征分析数量有限且耐药性数据较少,本研究旨在评估该地区循环耐药突变的流行情况。

方法

在刚果共和国的四个半城市地区招募了有抗逆转录病毒治疗经验的艾滋病毒阳性患者。采集血浆样本并提取病毒RNA。按照波尔多大学医院的一般诊断程序,通过逆转录定量聚合酶链反应(RT-qPCR)评估每位患者的病毒载量。最后,对该区域进行桑格测序后进行耐药基因分型和系统发育分析。

结果

观察到HIV-1毒株具有高度多样性,有许多重组形式。确定了RT和PR基因中的耐药突变,并将其与高效抗逆转录病毒治疗(HAART)相关联。由于刚果共和国的治疗中很少使用整合酶抑制剂,因此还确定了治疗前整合酶耐药突变的流行情况。有趣的是,观察到的突变很少。

结论

我们证实了刚果共和国HIV-1的高度多样性。大多数患者出现了对NRTIs、NNRTIs和PIs产生耐药性的突变积累。尽管如此,未发现与耐药性相关的整合酶突变,这表明将整合酶抑制剂引入治疗对刚果共和国的患者将非常有益。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c83a/8620905/cae770add142/microorganisms-09-02355-g001.jpg

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