2018年我国部分省份抗病毒治疗前HIV-1整合酶抑制剂耐药流行情况

A survey on integrase inhibitor related resistance in HIV-infected persons before antiretroviral treatment in China in 2018

目的了解我国2018年部分省份抗病毒治疗前HIV感染者中整合酶抑制剂的耐药株流行情况。方法在我国不同区域的6个省份,收集部分2018年抗病毒治疗前HIV感染者血浆样本,提取病毒基因组核糖核酸,RT-PCR扩增整合酶基因片段并测序,利用进化树和HIVdb数据库,分别进行HIV亚型及耐药分析,并比较不同亚型间整合酶抑制剂相关的耐药遗传屏障差异。结果共获得序列755条,其中流行重组亚型CRF07_BC占35.9%(271例)、CRF01_AE为34.3%(259例)、CRF08_BC占15.1%(114例)、CRF55_01B占2.8%(21例)和B′_(CN)占1.7%(13例),其他重组亚型占10.2%(77例);整合酶抑制剂相关耐药突变的样本有6例,耐药率为0.8%(6例),其中1例对拉替拉韦(RAL)高度耐药,其余5例均对艾维雷韦和RAL低度耐药。相比欧美B亚型标准株HXB2,我国CRF01_AE、CRF07_BC、CRF08_BC和CRF55_01B亚型共有24个固有突变位点;与欧美B亚型比较,CRF07_BC在T66K位点上具有较高耐药遗传屏障,CRF01_AE、CRF08_BC和CRF55_01B在G140S、G140C位点上具有较高的耐药遗传屏障。结论我国2018年部分省份治疗前人群HIV-1整合酶抑制剂耐药毒株流行水平较低,主要流行重组亚型相比欧美B亚型具有较高的耐药遗传屏障。

Objective To investigate the prevalence of integrase inhibitor related resistance in HIV-infected persons before antiretroviral treatment(ART) in China in 2018. Methods HIV-infected patients were consecutively selected prior to ART in six provinces located in the southeast and northwestern China. Plasma samples were collected, on which HIV genomic RNA was extracted. A fragment of HIV integrase region was amplified by nested RT-PCR and sequenced. Based on the obtained sequences, HIV-1 subtypes were determined by phylogenetic analyses by using Fasttree2.0, and integrase inhibitor related resistance mutations were identified by using Stanford HIVdb. Genetic barriers for specific resistance mutations of major circulating recombinant forms were calculated and compared with B prevailing in the western countries. Results A total of 755 sequences were obtained, 35.9%(271) of which were CRF07_BC, followed by CRF01_AE(34.3%, 259), CRF08_BC(15.1%,114), CRF55_01B(2.8%, 21), B′_(CN)(1.7%, 13), and other strains(10.2%,77).There were 6 cases of integrase inhibitor related resistance, with the resistance rate of 0.8%(6). One harbored resistance to RAL at high level, and other five were resistant to EVG and RAL at low levels. In contrast with HXB2, the reference strain of subtype B,totally 12 subtype-specific polymorphisms were found in CRF01_AE, CRF07_BC, CRF08_BC and CRF55_01B. As compared to subtype B strains, CRF07_BC had a higher genetic barrier to produce T66 K resistance mutation, and CRF01_AE, CRF08_BC and CRF55_01B had higher genetic barriers to G140 S and G140 C mutations. Conclusion The prevalence of integrase inhibitor related resistance is relatively low among HIV/AIDS patients before ART. The major CRFs in China have higher genetic barriers to some resistance mutations in integrase domain.