Public Health Implications of HIV Transmission Networks

艾滋病毒传播网络对公共卫生的影响

• 批准号: 9063466
• 负责人: Joel Okrent Wertheim
• 金额: $ 13.35万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-06-04 至 2019-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9063466
• 关键词: Address; Age; Anti-Retroviral Agents; Biology; Clinical; Clinical Research; Clinical Trials; Clinical Trials Design; Communities; Computer software; Data; Development; Drug resistance; Epidemic; Epidemiology; Evolution; Future; Genetic; Genetic Variation; Genotype; Goals; HIV; HIV Infections; Health; Hispanics; Human; Human immunodeficiency virus test; Immune response; Incidence; Individual; Intervention; Light; Link; Measures; Mental Health; Methods; Modeling; Molecular; Molecular Evolution; Monitor; Nature; Network-based; New York City; Online Systems; Outcome; Pathway Analysis; Patients; Pattern; Phylogenetic Analysis; Positioning Attribute; Prevention; Prevention strategy; Preventive Clinical Trial; Prophylactic treatment; Protocols documentation; Public Health; Recording of previous events; Research Personnel; Research Project Grants; Risk Factors; Scientist; Structure; Testing; Therapeutic; Time; Translational Research; Treatment Efficacy; Treatment Failure; Vaccination; Vaccine Design; Viral; Virus; Work; acquired drug resistance; antiretroviral therapy; base; computerized tools; cytotoxic; effective therapy; improved; insight; men who have sex with men; migration; neutralizing antibody; pandemic disease; pathogen; programs; public health research; reconstruction; simulation; skills; success; tool; transmission process; treatment strategy; treatment trial; virus genetics

DESCRIPTION (provided by applicant): HIV is a rapidly evolving pathogen, which results in nearly unique viral genetic sequence in every infected patient. This rapid evolution complicates vaccine design and antiretroviral therapy. However, changes in the genetic sequence can also be used to reconstruct the transmission history of the virus. Phylogenetic approaches have proven useful for understanding the origins, diversification, and worldwide migration of HIV. However, the potential for molecular evolutionary analysis to be utilized for public health goals remains underappreciated and underexplored. Previous work on the nature of HIV transmission networks suggests that individuals in the most highly connected parts of the network have the greatest potential to transmit virus in the future. Methods. In this application, HIV sequences that were acquired during drug- resistance surveillance by the New York City Department of Health and Mental Hygiene (NYC-DOHMH) will be used to construct the HIV transmission network in New York City. By identifying infected individuals whose viral sequences are highly similar, potential transmission partners can be identified and linked to construct a transmission network. Simulations of intervention (antiretroviral treatment, therapeutic vaccination, pre- exposure prophylaxis [PrEP], etc), targeted at the most highly connected individuals across this network will be performed and compared to simulations of random antiretroviral intervention. The goal of these simulations is to identify network-informed targeted intervention strategies that could reduce the incidence of HIV infection. Additionally, simulated clinical preventive trials wil also be performed across the NYC-DOHMH network to develop network-informed metrics, methods, and protocols to test for reduced transmission in a clinical preventative trial. Finally, this same network construction approach will be applied to all publicly available HIV sequences to develop a surveillance tool which will allow other researchers to rapidly determine how their generated HIV sequences fit into the global HIV transmission network. Conclusions. These findings will demonstrate how HIV transmission networks can be used to guide effective treatment strategies, improve clinical trial design, and monitor the progression of the pandemic.

描述（由申请人提供）：HIV是一种快速发展的病原体，在每个感染患者中导致几乎独特的病毒遗传序列。这种快速进化使疫苗设计和抗逆转录病毒疗法复杂化。但是，遗传序列的变化也可以用于重建病毒的传播病史。系统发育方法已被证明可用于了解艾滋病毒的起源，多样化和全球迁移。但是，用于公共卫生目标的分子进化分析的潜力仍未得到充分的评价和未经反映。先前关于艾滋病毒传播网络性质的工作表明，网络中最高度连接的部位中的个人将来具有传播病毒的最大潜力。方法。在此应用中，纽约市卫生与精神卫生部（NYC-DOHMH）在耐药性监测期间获得的HIV序列将用于在纽约市构建HIV传输网络。通过确定病毒序列高度相似的感染个体，可以识别潜在的传输伙伴并将其链接到构建传输网络。将进行干预措施（抗逆转录病毒治疗，治疗疫苗接种，预防前预防[PREP]等），针对该网络中最高度连接的个体，并将其与随机抗逆转录病毒干预的模拟进行比较。这些模拟的目的是确定具有网络信息的目标干预策略 可以减少艾滋病毒感染的发生率。此外，还将在NYC-DOHMH网络上进行模拟的临床预防试验，以开发网络知识的指标，方法和方案，以测试临床预防试验中传播的降低。最后，这种相同的网络构建方法将应用于所有公开可用的HIV序列，以开发一种监视工具，该工具将使其他研究人员能够迅速确定其生成的HIV序列如何适合全球HIV传输网络。结论。这些发现将证明如何使用HIV传播网络来指导有效的治疗策略，改善临床试验设计并监测大流行的进展。