Phylodynamic Analysis of HIV Transmission Clusters in Kazakhstan for Targeted Interventions

对哈萨克斯坦艾滋病毒传播群进行系统动力学分析以进行有针对性的干预

• 批准号: 10212364
• 负责人: Syed Ali
• 金额: $ 6.4万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-07-15 至 2022-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10212364
• 关键词: Acquired Immunodeficiency Syndrome; Address; Africa; Asians; Automobile Driving; Award; Base Sequence; Behavior; Behavioral; Blood specimen; Central Asia; Characteristics; Clinical; Cluster Analysis; Collaborations; Collection; Communities; Computer Analysis; Consent; DNA; DNA Sequence; Data; Databases; Drug resistance; Drug usage; Epidemic; Epidemiology; Exhibits; Female; Future; Gender; Genes; Genetic; Genetic Variation; Genotype; Goals; Government; Grant; HIV; HIV Infections; HIV Seropositivity; HIV drug resistance; HIV-1; Harm Reduction; Heterosexuals; Infection; Injectable; Injecting drug user; International; Intervention; Kazakhstan; Link; Measures; Migrant; Modeling; Molecular; Molecular Epidemiology; Molecular Virology; Movement; Mutation; Needle Sharing; Participant; Pattern; Persons; Phylogenetic Analysis; Population; Populations at Risk; Prevalence; Prevention; Prevention program; Questionnaires; RNA; Recombinants; Recording of previous events; Research; Resistance; Resources; Risk; Risk Behaviors; Risk Factors; Risk Reduction; Sampling; Science; Services; Sexual Partners; Source; Statistical Models; Structure; Subgroup; Time; TimeLine; Travel; Universities; Variant; Woman; base; central database; demographics; disorder control; disorder prevention; drug resistant virus; high risk; high risk behavior; high risk population; innovation; insight; male; men who have sex with men; molecular sequence database; open source; pol genes; profiles in patients; programs; prophylactic; prospective; reconstruction; skills; social; sociodemographics; spatiotemporal; tool; transmission process; trend; viral RNA; virus genetics

PROJECT SUMMARY The HIV epidemic in Central Asia, including Kazakhstan was originally confined largely to persons who inject drugs (PWID), but is now spreading through sexual- and migrant-associated transmissions. Central Asia represents the world's most rapidly growing HIV epidemic region. Phylogenetic transmission clusters, composed of genetically similar HIV sequences (<1.5% diversity), represent recently-acquired/rapidly- transmitting infections (transmission “hotspots”). Our objective is to identify PWID-associated currently at-risk populations, sothey may be linked to services expeditiously.Our specific aims are: 1. Obtain sequences from well-characterized Kazakhstani HIV-infected blood samples from PWID and other high risk persons for phylodynamic and statistical modeling of HIV transmission clusters: To achieve this we will: a) Analyze previously generated 800 HIV pol sequences, and prospectively collect 400 blood samples, from consenting HIV-positive PWID and other high-risk groups, including men who have sex with men (MSM), heterosexuals, and male/female sexual partners; b) Administer a validated questionnaire to 400 consenting participants to characterize gender, sexual/social contacts, travel history, and risk behaviors; c) Include the same data for the above-mentioned 800 HIV historic samples collected and previously characterized by our collaborators; d) Extract HIV RNA/DNA from the prospective blood samples to carry out amplification and sequencing of the HIV pol gene. 2. We will use these HIV DNA sequences and linked questionnaire data to identify PWID-associated HIV transmission clusters and common clinical, sociodemographic and behavioral characteristics to focus resources towards the most relevant settings/high-risk behaviors. These clusters will be elucidated by: a) Using phylogenetic analysis to identify HIV subtypes/recombinant forms; b) Determining profiles of drug resistance and trends of its spatiotemporal transmission; c) Using genetic distance to the closest sequence as a measure of clustering and questionnaire data to identify subpopulations exhibiting rapid transmission; d) Using our prospectively generated 400 HIV sequences along with historic 800 Kazakhstani (and central Asian sequences obtained from open-access databases) to determine whether identified transmission clusters are newly emerging and/or rapidly expanding, and e) Inferring intra-Kazakhstan and Central Asian movements of HIV-1 by applying structured coalescent phylogenetic models. These analyses will be cross-confirmed using the open-source near real-time tracking platform, nextHIV, that performs automated alignment, subtyping, genotypic resistance determination, phylogenetic reconstruction and genetic distance clustering. The ultimate goal of our R03 small grant is to provide evidence regarding transmission hotspots that will help target emerging/expanding transmission clusters, stimulating both HIV control and prevention, and HIV molecular virology research in Kazakhstan and elsewhere in Central Asia.

项目总结 包括哈萨克斯坦在内的中亚地区的艾滋病毒疫情最初主要限于注射艾滋病毒的人。 毒品(PWID)，但现在正在通过与性和移民相关的传播传播。中亚 代表着世界上增长最快的艾滋病毒流行地区。系统发育传播群， 由遗传相似的HIV序列组成(&lt；1.5%的多样性)，代表最近获得的/迅速- 传播感染(传播“热点”)。我们的目标是确定与PWID相关的当前处于危险之中的 我们的具体目标是：1.获得序列 来自具有良好特征的哈萨克斯坦HIV感染血液样本，来自PWID和其他高危人群 艾滋病毒传播集群的系统动力学和统计建模人员：为实现这一目标，我们将： A)分析以前产生的800个艾滋病毒轮询序列，并预期收集400份血液样本， 同意艾滋病毒阳性的PWID和其他高危人群，包括男男性行为者(MSM)， 异性恋者和男性/女性性伴侣；b)向400名同意的人发放有效问卷 确定性别、性/社会接触、旅行史和危险行为特征的参与者；c)包括 上述800艾滋病毒历史样本的相同数据，之前由我们的 合作者；d)从预期的血液样本中提取艾滋病毒RNA/DNA以进行扩增和 人类免疫缺陷病毒Poll基因的测序。2.我们将使用这些HIV DNA序列和关联的问卷数据 确定与PWID相关的HIV传播群和常见的临床、社会人口学和 行为特征，将资源集中到最相关的环境/高风险行为。这些 集群将通过：a)使用系统发育分析来确定艾滋病毒亚型/重组形式；b) 确定耐药情况及其时空传播趋势；c)利用基因 距离最近序列的距离，作为聚类和问卷数据的衡量标准，以确定子群体 显示出快速传播；d)使用我们预期产生的400个艾滋病毒序列以及历史上的800个 哈萨克斯坦(和从开放获取数据库获得的中亚序列)，以确定是否 已确定的传播集群是新出现的和/或迅速扩大的，以及e)推断哈萨克斯坦境内 通过应用结构化的联合系统发育模型研究艾滋病毒-1在中亚的运动。这些 分析将使用开源的近实时跟踪平台nextHIV进行交叉确认， 执行自动比对、分型、基因耐药性测定、系统发育重建和 遗传距离聚类。我们R03小额赠款的最终目的是提供关于 传播热点将有助于针对新兴/不断扩大的传播集群，刺激两种艾滋病毒 哈萨克斯坦和中亚其他地区的控制和预防以及艾滋病毒分子病毒学研究。

项目成果

HBV Prevention and Treatment in Countries of Central Asia and the Caucasus.

• DOI: 10.3390/v12101112
• 发表时间: 2020-09-30
• 期刊: Viruses
• 作者: Amerzhanov D;Suleimenova I;Davlidova S;Nugmanova Z;Ali S
• 通讯作者: Ali S

Repurposing potential of posaconazole and grazoprevir as inhibitors of SARS-CoV-2 helicase.

• DOI: 10.1038/s41598-021-89724-0
• 发表时间: 2021-05-13
• 期刊: Scientific reports
• 影响因子: 4.6
• 作者: Abidi SH;Almansour NM;Amerzhanov D;Allemailem KS;Rafaqat W;Ibrahim MAA;la Fleur P;Lukac M;Ali S
• 通讯作者: Ali S

Origin and evolution of HIV-1 subtype A6.

• DOI: 10.1371/journal.pone.0260604
• 发表时间: 2021
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Abidi SH;Aibekova L;Davlidova S;Amangeldiyeva A;Foley B;Ali S
• 通讯作者: Ali S

Multi-Subunit SARS-CoV-2 Vaccine Design Using Evolutionarily Conserved T- and B- Cell Epitopes.

• DOI: 10.3390/vaccines9070702
• 发表时间: 2021-06-26
• 期刊: Vaccines
• 影响因子: 7.8
• 作者: Akbay B;Abidi SH;Ibrahim MAA;Mukhatayev Z;Ali S
• 通讯作者: Ali S

Hepatitis B, Hepatitis C, tuberculosis and sexually-transmitted infections among HIV positive patients in Kazakhstan.

• DOI: 10.1038/s41598-021-92688-w
• 发表时间: 2021-06-29
• 期刊: Scientific reports
• 影响因子: 4.6
• 作者: Mukhatayeva A;Mustafa A;Dzissyuk N;Issanov A;Bayserkin B;Vermund SH;Ali S
• 通讯作者: Ali S