英国耐药的HIV-1传播减低

据医学空间网5月18日报道（原载AIDS 2007 May 11：21（8）：1035—9），调查表明近来英国传播的药物耐受（TDR）的趋势减低。[第一段]     

淮安市新报告HIV-1感染者的分子传播网络特征研究

目的 了解淮安市新报告人感染HIV-1毒株的流行特征、亚型及分子传播网络特征。方法 采集淮安籍HIV-1确证阳性感染者血液标本,利用巢式(RT-)PCR方法扩增pol基因片段,测序并构建分子传播网络。结果 淮安市新报告人感染的HIV-1基因亚型有9种,分别为CRF01＿AE (38.5%,47/122)、CRF07＿BC (38.5%,47/122)、CRF67＿01B (8.2%,10/122)、CRF68＿01B (4.9%,6/122)、B (3.3%,4/122)、CRF08＿BC (3.3%,4/122)、CRF55＿01B (1.6%,2/122)、CRF85＿BC (0.8%,1/122)和CRF52＿01B (0.8%,1/122)。60条pol基因序列形成10个分子传播簇,入网率为49.2%,其中最大的分子传播网络由CRF07＿BC基因型构成。logistic回归分析显示已婚有配偶(与丧偶相比,OR=0.242,95%CI:0.006-0.972)、同性传播(与异性传播相比,OR=2.113,95%CI:1.020-4.377)、基因型CRF07＿BC (与其他重组型...     

安徽省阜阳市新报告HIV感染者耐药及分子传播网络研究

目的 分析安徽省阜阳市2020-2021年新报告HIV感染者主要亚型毒株的分子流行特征及传播网络情况,为当地制订有效的干预措施提供依据。方法 2020年1月至2021年12月共收集阜阳市新报告感染HIV-1血液样本589份,扩增pol基因和测序,运用美国斯坦福大学耐药数据库进行耐药突变分析,构建系统进化树,提取传播网络并分析其特征,对研究对象进入网络的相关因素进行分析。结果 成功扩增获得589名HIV感染者的pol区基因序列,主要的亚型为CRF07＿BC(34.8%),B(30.4%)和CRF01＿AE(22.4%),新报告感染者总体耐药率为8.6%。三个主要亚型分别以0.5%作为基因距离阈值构建了分子传播网络,入网率分别为B(41.3%)、CRF07＿BC(34.6%)和CRF01＿AE(20.5%)。对进入网络的影响因素进行分析,多因素Logistic回归结果显示,年龄>50岁（与<30岁相比,a OR=2.419,95%CI:1.189～4.921）、CRF07＿BC（与CRF01＿AE相比,a OR=1.875,95%CI:1.085～3.242）、B亚型（与CRF...     

HIV-1基因变异与耐药之间的关系研究现况

HIV-1以其高突变率、高重组率和高复制率的生物学特性,使得患者体内的病毒成为复杂的准种,给艾滋病的诊断、治疗和疫苗的研制带来众多难题。高效抗逆转录病毒联合疗法的使用降低了艾滋病患者的病死率,然而在高速复制、高度遗传变异和药物选择压力的作用下,日益严重的耐药问题削弱了其抑制病毒复制的作用,降低了抗病毒治疗的效果。本文综述了HIV-1常见的基因变异特点与耐药之间关系的研究进展,以期对临床制订抗HIV-1药物方案、发展新的抗HIV-1策略带来指导意义。     

龙州县HIV-1分子传播网络特征及影响因素分析

目的 分析广西崇左市龙州县HIV/AIDS患者中HIV-1分子传播网络特征,并探讨网络形成的相关影响因素。方法 对2003-2021年龙州县报告的HIV/AIDS患者采集血样,通过DNA提取、pol区扩增、测序及序列整理,使用HIV-TRACE筛选最佳基因距离及构建分子传播网络。对分类资料进行χ²检验,使用Logistic回归模型分析入网和高连接度个体的影响因素。结果 共收集到545份研究样本,成功获得361例HIV/AIDS患者的HIV-1 pol区序列。HIV亚型以CRF01＿AE(88.09%)为主,其次为CRF07＿BC(5.26%)和CRF08＿BC(3.88%)。多因素结果显示,无性病史(OR=3.238,95%CI:1.134～10.642)、已婚/同居(OR=1.953,95%CI:1.03～3.758)的患者更容易入网;年龄≥50岁(OR=2.656,95%CI:1.394～5.109)的患者更容易成为该网络的高连接度个体,而高中/中专及以上(OR=0.251,95%CI:0.057～0.784)更不容易成为高连接度个体。结论 2003-2021...     

黑龙江省2018年新发现HIV-1感染者毒株亚型分子簇及耐药情况

目的 分析黑龙江省HIV-1感染者的毒株亚型构成、分子簇形成和耐药株流行情况.方法 对2018年1-6月期间新诊断的、尚未进行抗病毒治疗的黑龙江省HIV-1感染者,采集血样、提取病毒RNA,采用反转录聚合酶链式反应(RT-PCR)/巢式PCR方法扩增HIV-1 pol基因,测序后进行生物信息学分析.结果 获得157例H...     

2018年至2019年浙江省绍兴市新确证人类免疫缺陷病毒1型感染者的分子传播网络特征分析

目的:分析浙江省绍兴市新确证人类免疫缺陷病毒1型(human immunodeficiency virus type 1,HIV-1)感染者传播关系的分子网络特征,为疫情流行趋势和防治提供依据。方法:纳入2018年8月至2019年12月绍兴市新确证未经抗病毒治疗的423份HIV-1感染/艾滋病病例血液样本,获得375份...     

甘肃省部分地区2020-2021年新报告HIV/AIDS患者治前耐药及分子传播网络特征分析

目的 分析甘肃省部分地区新报告HIV/AIDS患者分子传播网络特征,为精准干预相关人群中HIV-1传播提供实验室依据。方法 反转录和巢式PCR扩增样本pol区基因并测序,采用MEGA 7.0软件构建系统进化树分析亚型,通过美国斯坦福大学HIV耐药数据库在线软件工具分析耐药突变位点,Hyphy和Cytoscape 3.9.1软件生成分子网络,Logistic回归模型对入网率的影响因素进行分析。结果 收集甘肃省部分地区2020-2021年新报告病例血浆样本331份,成功获得pol区基因序列303条,共发现11种亚型和流行重组型,主要为CRF07＿BC(58.1%)、CRF01＿AE(21.1%)、B(6.9%)和CRF55＿01B (5.3%)。治疗前耐药率为4.0%,NNRTI类耐药率最高为3.3%,主要耐药位点是K103 N/S (1.7%)。分子网络最适基因距离为1.2%,在此基因距离时共形成33个分子簇,91条序列入网,入网率为30.0%。对进入网络的影响因素进行分析,多因素Logistic回归结果显示,CRF07＿BC（与CRF01＿AE相比）、河西地区（与陇东南地区相比）更容易...     

2018年广西崇左边境ART人群HIV-1分子网络特征分析

目的 构建广西边境崇左市四个边境县接受ART的HIV/AIDS患者的本底分子网络并识别重点人群,为当地防控艾滋病进行重点干预提供依据.方法 纳入2018年1-9月在广西崇左市大新县、宁明县、凭祥市、龙州县四个地区进行常规CD4细胞检测的在治HIV/AIDS患者作为研究对象,并收集研究对象基本信息,使用HIV-TRACE...     

浙江省北部区域人类免疫缺陷病毒1型的分子传播特征

目的:通过构建浙江省北部区域(嘉兴市和湖州市)人类免疫缺陷病毒1型(human immunodeficiency virus type 1,HIV-1)流行株的分子传播网络,探索HIV-1在该区域的传播特征。方法:以2017年嘉兴市和湖州市新诊断的371例人类免疫缺陷病毒(human immunodeficiency ...     

Molecular Dynamics Free Energy Simulations Reveal the Mechanism for the Antiviral Resistance of the M66I HIV-1 Capsid Mutation

While drug resistance mutations can often be attributed to the loss of direct or solvent-mediated protein−ligand interactions in the drug-mutant complex, in this study we show that a resistance mutation for the picomolar HIV-1 capsid (CA)-targeting antiviral (GS-6207) is mainly due to the free energy cost of the drug-induced protein side chain reorganization in the mutant protein. Among several mutations, M66I causes the most suppression of the GS-6207 antiviral activity (up to ~84,000-fold), and only 83- and 68-fold reductions for PF74 and ZW-1261, respectively. To understand the molecular basis of this drug resistance, we conducted molecular dynamics free energy simulations to study the structures, energetics, and conformational free energy landscapes involved in the inhibitors binding at the interface of two CA monomers. To minimize the protein−ligand steric clash, the I66 side chain in the M66I−GS-6207 complex switches to a higher free energy conformation from the one adopted in the apo M66I. In contrast, the binding of GS-6207 to the wild-type CA does not lead to any significant M66 conformational change. Based on an analysis that decomposes the absolute binding free energy into contributions from two receptor conformational states, it appears that it is the free energy cost of side chain reorganization rather than the reduced protein−ligand interaction that is largely responsible for the drug resistance against GS-6207.     

Molecular Epidemiological Analysis of the Origin and Transmission Dynamics of the HIV-1 CRF01_AE Sub-Epidemic in Bulgaria

HIV-1 subtype CRF01_AE is the second most predominant strain in Bulgaria, yet little is known about the molecular epidemiology of its origin and transmissibility. We used a phylodynamics approach to better understand this sub-epidemic by analyzing 270 HIV-1 polymerase (pol) sequences collected from persons diagnosed with HIV/AIDS between 1995 and 2019. Using network analyses at a 1.5% genetic distance threshold (d), we found a large 154-member outbreak cluster composed mostly of persons who inject drugs (PWID) that were predominantly men. At d = 0.5%, which was used to identify more recent transmission, the large cluster dissociated into three clusters of 18, 12, and 7 members, respectively, five dyads, and 107 singletons. Phylogenetic analysis of the Bulgarian sequences with publicly available global sequences showed that CRF01_AE likely originated from multiple Asian countries, with Vietnam as the likely source of the outbreak cluster between 1988 and 1990. Our findings indicate that CRF01_AE was introduced into Bulgaria multiple times since 1988, and infections then rapidly spread among PWID locally with bridging to other risk groups and countries. CRF01_AE continues to spread in Bulgaria as evidenced by the more recent large clusters identified at d = 0.5%, highlighting the importance of public health prevention efforts in the PWID communities.     

Drug Resistance Mechanism of M46I-Mutation-Induced Saquinavir Resistance in HIV-1 Protease Using Molecular Dynamics Simulation and Binding Energy Calculation

Drug-resistance-associated mutation in essential proteins of the viral life cycle is a major concern in anti-retroviral therapy. M46I, a non-active site mutation in HIV-1 protease has been clinically associated with saquinavir resistance in HIV patients. A 100 ns molecular dynamics (MD) simulation and MM-PBSA calculations were performed to study the molecular mechanism of M46I-mutation-based saquinavir resistance. In order to acquire deeper insight into the drug-resistance mechanism, the flap curling, closed/semi-open/open conformations, and active site compactness were studied. The M46I mutation significantly affects the energetics and conformational stability of HIV-1 protease in terms of RMSD, RMSF, Rg, SASA, and hydrogen formation potential. This mutation significantly decreased van der Waals interaction and binding free energy (∆G) in the M46I–saquinavir complex and induced inward flap curling and a wider opening of the flaps for most of the MD simulation period. The predominant open conformation was reduced, but inward flap curling/active site compactness was increased in the presence of saquinavir in M46I HIV-1 protease. In conclusion, the M46I mutation induced structural dynamics changes that weaken the protease grip on saquinavir without distorting the active site of the protein. The produced information may be utilized for the discovery of inhibitor(s) against drug-resistant HIV-1 protease.     

2018年新报告HIV-1感染者省际传播特征分析

目的 分析省际1 型艾滋病病毒(HIV-1)的传播特征,为实施精准防控进而减少HIV-1在我国的流行提供科学数据.方法 对2018年当年新报告的HIV-1感染者进行抽样调查.收集血样并提取病毒核糖核酸,获得pol区部分片段的序列,构建系统进化树.运用HIV-TRACE构建分子网络并筛选出跨省分子簇.结果 共调查31个省...