Pilot Study to Monitor HIV Cluster Dynamics and Active HIV sub-Epidemics in Real Time

实时监测艾滋病毒集群动态和活跃艾滋病毒亚流行病的试点研究

• 批准号: 9560096
• 负责人: VLADIMIR A NOVITSKY
• 金额: $ 9.32万
• 依托单位: HARVARD SCHOOL OF PUBLIC HEALTH
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-07-02 至 2018-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9560096
• 关键词: 16 year old; Bedside Testings; Botswana; Cluster Analysis; Complement; Data; Drops; Drug resistance; Enrollment; Epidemic; Genotype; Geographic Locations; Goals; HIV; HIV Genome; HIV drug resistance; Health; Health Policy; Hospital Referrals; Incidence; Individual; Intervention; Length; Link; Monitor; Newly Diagnosed; Outcome; Outcome Study; Participant; Phylogenetic Analysis; Phylogeny; Pilot Projects; Prevention; Public Policy; RNA; Reproduction; Resources; Sampling; Structure; Technology; Testing; Time; Validation; Viral Load result; Virus; aged; base; cost; nanopore; next generation sequencing; novel; real time model; real time monitoring; reproductive; response; success; time use; transmission process

Understanding local HIV sub-epidemics is key to eliminating the HIV epidemic. Real-time phylodynamics is critical, as only real-time monitoring of HIV transmission dynamics and identification of emerging HIV sub- epidemics could guide real-time public policy decisions. Results of this study will prove the feasibility of real- time monitoring of HIV transmission clusters in limited-resource settings. We hypothesize that newly diagnosed individuals with detectable HIV RNA are disproportionately linked to active HIV sub-epidemics, i.e. clusters with effective reproductive number Re > 1.0. We will perform HIV genotyping in real time using novel nanopore MinION technology. This will allow us to assess phylogenetic linkages between individuals with detectable HIV RNA and active HIV sub-epidemics in real time. A model for real-time monitoring of HIV cluster dynamics will be the study outcome. Specific Aim 1. Real-time HIV genotyping: Feasibility of real-time HIV genotyping in the field, and results validation. We will enroll 750 participantsnewly diagnosed individuals and people initiating ART through referrals. We will perform point-of-care testing of viral load, test the feasibility of real-time HIV genotyping in the field, perform long-range HIV amplification, barcoding, and sequencing using novel nanopore MinION technology in the field, and generate 667 (up to 750) near full-length HIV genomes using nanopore technology in the field in real time. To validate results, we will compare data obtained using nanopore MinION in the field and next-generation sequencing data generated by Illumina HiSeq. Specific Aim 2. Real-time phylogenetic cluster analysis: Feasibility of monitoring HIV transmission clusters and active HIV sub-epidemics in real time. To assess HIV cluster dynamics in real time, we will infer phylogenies of newly generated HIV sequences (n=667; up to 750). We will enumerate HIV transmission clusters by identifying phylogenetically distinct HIV sub-epidemics. We will reconstruct dated phylogenies and identify active HIV sub-epidemics—i.e., those with an effective reproduction number Re  1.0. We will estimate linkages between newly diagnosed individuals with detectable viral load and active HIV sub-epidemics. We will perform HIV drug-resistance analysis and return the results to clinicians and participants in real time. The proposed study has the potential to develop a model for real-time monitoring of HIV transmission clusters, and for identifying emerging HIV sub-epidemics in real time. The study will demonstrate that real-time monitoring of HIV transmission clusters is feasible, will validate the results, and will determine whether real- time drug-resistance testing is realistic and could be performed in the field. We will test whether the cost of real-time HIV genotyping in the field could be dropped to $34 per sample.

了解局部艾滋病毒亚表皮学是消除艾滋病毒流行病的关键。实时系统动力学是 批判性，仅是对HIV传播动态的实时监测和新兴HIV子的鉴定 情节可以指导实时公共政策决策。这项研究的结果将证明相关的可行性 在限量资源设置中对艾滋病毒传输群集的时间监视。 我们假设新诊断的患有可检测的HIV RNA的个体是不成比例的 为了活跃的HIV亚表皮，即具有有效生殖数的簇Re> 1.0。我们将表演 实时使用新型纳米虫牛仔技术实时进行HIV基因分型。这将使我们能够评估系统发育 实时可检测到的HIV RNA的个体与主动HIV亚发育学的个体之间的联系。一个模型 对HIV聚类动力学的实时监测将是研究结果。 特定目的1。实时HIV基因分型：现场实时HIV基因分型的可行性，以及 结果验证。我们将注册750名参与者被诊断为个人，人们发起Art 通过推荐。我们将对病毒负荷进行护理点测试，测试实时HIV的可行性 在现场的基因分型，使用新型纳米孔进行远程HIV扩增，条形码和测序 该领域的奴才技术，并使用纳米孔在全长艾滋病毒基因组附近生成667（高达750） 实时的技术。为了验证结果，我们将比较使用纳米孔奴才获得的数据 在Illumina Hiseq生成的现场和下一代测序数据中。 特定目标2。实时系统发育集群分析：监测HIV传播的可行性 集群和活跃的HIV亚发育学实时。为了实时评估HIV簇动力学，我们将 推断新生成的HIV序列的系统发育（n = 667；高达750）。我们将列举艾滋病毒传播 通过识别系统发育不同的HIV亚发育学来识别簇。我们将重建陈旧的系统发育和 识别活跃的HIV亚发育学-I.E。，有效繁殖数的人re1.0。我们将估计 新诊断的具有可检测的病毒负荷的个体与主动HIV亚表皮学之间的联系。我们将 进行艾滋病毒抗药性分析，并将结果实时归还给临床医生和参与者。 拟议的研究有可能开发用于实时监测HIV传播簇的模型， 并用于实时识别新兴的HIV次发育。该研究将证明实时 对HIV传播簇的监测是可行的，将验证结果，并将确定是否实现 时间抗药性测试是现实的，可以在现场进行。我们将测试成本是否 该领域的实时HIV基因分型可以降至每个样本34美元。