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

基本信息

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
项目类别：
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

项目摘要

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.

项目概要包括哈萨克斯坦在内的中亚地区的艾滋病毒流行最初主要局限于注射者毒品（注射吸毒者），但现在正在通过性传播和移民相关的中亚传播。代表世界上增长最快的艾滋病毒流行区域。由遗传相似的 HIV 序列（<1.5% 多样性）组成，代表最近获得/快速- 传播感染（传播“热点”）。我们的目标是确定目前存在与吸毒者相关的风险。人群，以便他们可以迅速与服务联系起来。我们的具体目标是： 1. 获取序列来自吸毒者和其他高风险人群的经过充分鉴定的哈萨克斯坦艾滋病毒感染者血液样本艾滋病毒传播集群的系统动力学和统计模型的人员：为了实现这一目标，我们将： a) 分析之前生成的 800 个 HIV pol 序列，并前瞻性地收集 400 个血液样本，同意 HIV 阳性吸毒者和其他高危人群，包括男男性行为者 (MSM)，异性恋者和男性/女性性伴侣；b) 对 400 名同意的人进行经过验证的调查问卷参与者描述性别、性/社会接触、旅行史和风险行为；我们之前收集并表征的上述 800 个 HIV 历史样本的相同数据 d) 从预期的血液样本中提取 HIV RNA/DNA 进行扩增和 HIV pol 基因测序 2. 我们将使用这些 HIV DNA 序列和关联的问卷数据。确定与吸毒者相关的艾滋病毒传播集群以及常见的临床、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。将通过以下方式阐明簇： a) 使用系统发育分析来识别 HIV 亚型/重组形式；确定耐药性概况及其时空传播趋势 c) 利用遗传；到最近序列的距离作为聚类和问卷数据的衡量标准，以识别亚群 d) 使用我们预期生成的 400 个 HIV 序列以及历史上的 800 个序列哈萨克斯坦（以及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和/或迅速扩大的，并且 e) 推断哈萨克斯坦内部通过应用结构化合并系统发育模型研究 HIV-1 的中亚运动。分析将使用开源近实时跟踪平台 nextHIV 进行交叉确认，执行自动比对、亚型分析、基因型抗性测定、系统发育重建和我们 R03 小额资助的最终目标是提供有关遗传距离聚类的证据。传播热点将有助于瞄准新兴/扩大的传播集群，刺激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

期刊论文数量（8）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

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

使用进化保守的 T 细胞和 B 细胞表位设计多亚基 SARS-CoV-2 疫苗。

DOI：
发表时间：
2021-06-26
期刊：
影响因子：
7.8
作者：
Akbay, Burkitkan;Abidi, Syed Hani;Ibrahim, Mahmoud A A;Mukhatayev, Zhussipbek;Ali, Syed
通讯作者：
Ali, Syed

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

中亚和高加索国家的乙型肝炎预防和治疗。

DOI：
发表时间：
2020-09-30
期刊：
影响因子：
0
作者：
Amerzhanov, Daulet;Suleimenova, Indira;Davlidova, Salima;Nugmanova, Zhamilya;Ali, Syed
通讯作者：
Ali, Syed

HBV S antigen evolution in the backdrop of HDV infection affects epitope processing and presentation.

HDV 感染背景下的 HBV S 抗原进化影响表位加工和呈递。

DOI：
发表时间：
2021-06
期刊：
影响因子：
12.7
作者：
Sajjad, Mehwish;Ali, Syed;Baig, Samina;Sharafat, Shaheen;Khan, Bilal Ahmed;Khan, Saeed;Mughal, Nouman;Abidi, Syed Hani
通讯作者：
Abidi, Syed Hani

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

重新利用泊沙康唑和格拉佐韦作为 SARS-CoV-2 解旋酶抑制剂的潜力。

DOI：
发表时间：
2021-05-13
期刊：
影响因子：
4.6
作者：
Abidi, Syed Hani;Almansour, Nahlah Makki;Amerzhanov, Daulet;Allemailem, Khaled S;Rafaqat, Wardah;Ibrahim, Mahmoud A A;la Fleur, Philip;Lukac, Martin;Ali, Syed
通讯作者：
Ali, Syed

Origin and evolution of HIV-1 subtype A6.

HIV-1 A6 亚型的起源和进化。