新疆维吾尔自治区阿克苏地区艾滋病抗病毒治疗失败人群耐药及分子网络分析

Analysis of Drug Resistance and Molecular Network Among Patients with HIV/AIDS Who Had Virological Failure After Antiretroviral Therapy in Aksu Prefecture,Xinjiang Uygur Autonomous Region,China

了解新疆维吾尔自治区阿克苏地区艾滋病抗病毒治疗失败人群耐药及分子网络特征情况。收集2020⁃2021年新疆维吾尔自治区阿克苏地区6个县接受抗病毒治疗超过6个月且HIV⁃1病毒载量≥1000拷贝/mL的人群血样,获得HIV⁃1 pol基因区序列,使用MEGA 5.02软件构建系统进化树判定毒株亚型,利用美国斯坦福大学耐药数据库进行耐药判定,运用HyPhy 2.2.1软件和Cytoscape 3.2.1软件进行HIV分子网络分析。研究获得HIV⁃1 pol区基因序列817条,毒株亚型以CRF07_BC为主,占99.1%(810/817)。HIV⁃1耐药率为58.5%(478/817),非核苷类反转录酶抑制剂(NNRTI)类耐药率为53.0%(433/817),核苷类反转录酶抑制剂(NRTI)耐药率为18.8%(154/817),蛋白酶抑制剂(PI)耐药率为7.8%(64/817)。多因素Logistic回归模型分析结果显示,治疗前CD4+T淋巴细胞计数为350~499个/μL发生耐药的风险是<350个/μL的0.61倍(95%CI:0.41~0.91)、初始治疗方案含洛匹那韦/利托那韦(LPV/r)二线治疗方案的耐药风险是含替诺福韦(TDF)一线治疗方案的0.27倍(95%CI:0.12~0.61)、开始抗病毒治疗年份在2018⁃2020年耐药发生风险是<2018年的0.62倍(95%CI:0.44~0.87)。按1.5%基因距离阈值构建分子网络,入网率为49.1%(401/817),发现分子簇26个,其中96.2%(25/26)的簇中有耐药突变位点。男性入网风险高于女性。提示阿克苏地区艾滋病抗病毒治疗失败人群耐药率较高,耐药株在分子网络中成簇出现,应加强抗病毒治疗和随访管理质量,减少耐药发生及毒株传播。

Objective to investigate the prevalence and potential factors related with drug resistance among patients with HIV/AIDS who had virologic failure after antiretroviral therapy(ART)from six counties of Aksu prefecture in Xinjiang Uygur Autonomous Region,China and analyze the characteristics of the molecular network of the HIV strains.The blood samples were collected from 2020 to 2021,patients with HIV who received antiviral therapy beyond 6 months and the viral loads≥1000 copies/mL were included.HIV⁃1 pol fragment was amplified and sequenced.For HIV subtyping,phylogenetic tree was constructed using MEGA 5.02 software.Drug⁃resistant mutations were determined using the Stanford University HIV Drug Resistance Database.Molecular transmission network was analyzed using HyPhy 2.2.1 and Cytoscape 3.2.1 software.Results A total of 817 sequences were obtained.The most common subtype was CRF07_BC,accounting for 99.1%(810/817)of the HIV strains,and the rate of drug resistant was 58.5%(478/817).The rates of HIV drug resistance to nonnucleoside reverse transcriptase inhibitor(NNRTI),nucleoside reverse transcriptase inhibitor(NRTI),and protease inhibitor(PI)were 53.0%(433/817),18.8%(154/817),7.8%(64/817)respectively.Multivariate logistic regression showed that compared with a baseline CD4+T lymphocyte count of less than 350 cell/μL,CD4+T lymphocyte count between 350~499 cell/μL was 0.61 times(95%CI:0.41-0.91)likely to have drug resistance.Patients receiving Lopinavir/Ritonavir(LPV/r)⁃based initial regimens was 0.27 times(95%CI:0.12-0.61)likely to have drug resistance as compared with those with TDF based regimens.In addition,patients receiving ART between 2018 and 2020 was 0.62 times(95%CI:0.44~0.87)to get drug resistance compared with those receiving ART before 2018.There were 49.1%(401/817)of the HIV strains within molecular network based on 1.5%of gene distance threshold,and 26 clusters were found.The clusters which had drug resistance sequence were 96.2%(25/26).The molecular network access rate in male was higher than female.The rate of drug resistant was relatively high among people living with HIV/AIDS who had virological failure after ART in this area,and drug resistant sequences were transmitted as shown in clusters.The intervention and surveillance among these individuals should be strengthened,to decrease the risk of drug resistance and transmission.