Efficacy of ART to Interrupt HIV Transmission Networks

ART 阻断 HIV 传播网络的功效

• 批准号: 8658916
• 负责人: SUSAN JANET LITTLE
• 金额: $ 71.26万
• 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: 2014-05-12 至 2019-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8658916
• 关键词: AIDS prevention; Address; Affect; Alcohol or Other Drugs use; Anti-Retroviral Agents; Calibration; Communities; Computer Simulation; Confidentiality of Patient Information; Data; Demographic Factors; Disclosure; Drug resistance; Effectiveness; Epidemic; Epidemiological Factors; Epidemiology; Future; Growth; HIV; HIV Infections; HIV diagnosis; Heterosexuals; Hot Spot; Incidence; Individual; Infection; Information Networks; Intervention; Link; Measures; Methods; Molecular Epidemiology; Nature; Network-based; Participant; Persons; Population; Prevention; Prevention strategy; Preventive Intervention; Privacy; Prospective Studies; Public Health Applications Research; Randomized; Reporting; Research Infrastructure; Resources; Risk; Risk Estimate; Sample Size; Sampling Biases; Sexually Transmitted Diseases; Structure; Testing; Time; Treatment Efficacy; antiretroviral therapy; base; cohort; effective intervention; efficacy testing; innovation; insight; men who have sex with men; novel; patient privacy; population based; prospective; public health relevance; randomized trial; reproductive; simulation; statistics; theories; transmission process; virus genetics

Antiretroviral treatment (ART) markedly reduces the risk of HIV transmission between stable HIV discordant heterosexual partners and increasing ART use can effect "population-level" reductions in HIV incidence. Whether or not HIV prevention interventions, such as ART "Treatment as Prevention" (TasP) strategies can significantly reduce epidemic growth rates remains a matter of considerable debate, though current community-randomized TasP trials will require vast infrastructure and financial resources. Alternative, less resource-prohibitive approaches are needed, that ideally would also provide real-time insight into HIV transmission dynamics and be easily modified to address unique regional and epidemiological factors. Prospective studies of prevention and treatment interventions that target epidemiologic "hot spots" of HIV transmission may provide an opportunity to efficiently interrupt HIV transmission chains. Effective prevention interventions are particularly relevant in populations of men who have sex with men (MSM) since their incidence rates are disproportionately high compared to other risk groups. We propose to use molecular epidemiology and computational modeling to estimate in real time the risk of onward HIV transmission in newly HIV diagnosed persons. We have shown that by evaluating HIV sequences that are generated in 'real- time' after a participant is identified from our San Diego Primary HIV infection Cohort (SD PIC), a partial transmission network can be inferred rapidly and reliably, and this network can be leveraged to better measure the efficacy of treatments and interventions, correlates of transmission risk, and estimate the size and features of the San Diego HIV epidemic. The proposed study will also address concerns related to patient confidentiality, specifically - unintended disclosure of HIV status or a putative transmission link. We will develop sophisticated quantitative methods to preserve privacy prior to future consideration of potential public health applications. Our primary hypothesis is that the efficacy of HIV prevention interventions, such as TasP (i.e., ART), can be measured within a well-characterized MSM epidemic, using network statistics to assess real time changes in HIV transmission dynamics within the population. This proposal will address the following Specific Aims: 1) To infer the San Diego HIV transmission network using molecular epidemiology and use agent-based simulations to estimate features of the underlying infected population and efficacy of potential interventions, 2) To assess the potential of molecular epidemiology and network statistics to measure the efficacy of ART as a network-based prevention intervention, by comparing HIV transmission rates in persons who initiate early ART compared to those who either delay or decline ART, and 3) To develop and deploy privacy preserving methods for computing transmission network statistics. These same methods could be easily replicated in a prospective fashion across diverse HIV epidemics and could help to prioritize interventions within the scope of available resources.

抗逆转录病毒治疗（ART）显着降低了稳定的HIV不一致的HIV传播风险 异性恋伙伴和不断增加的艺术使用会影响艾滋病毒发病率的“人口水平”。 艾滋病毒预防干预措施，例如“预防治疗”（TASP）策略是否可以 显着降低流行病的增长率仍然是一个很大的争论，尽管目前 社区随机TASP试验将需要大量的基础设施和财务资源。替代方案，更少 需要采用资源过滤的方法，理想情况下，这也将提供对艾滋病毒的实时见解 传输动力学并易于修改以解决独特的区域和流行病学因素。 针对艾滋病毒的流行病学“热点”的预防和治疗干预措施的前瞻性研究 传播可能会提供有效中断艾滋病毒传播链的机会。有效的预防 干预措施在与男性发生性关系（MSM）的人群中特别重要 与其他风险组相比，发病率较高。我们建议使用分子 流行病学和计算建模实时估算艾滋病毒传播的风险 新近艾滋病毒诊断的人。我们已经表明，通过评估在“实现”中生成的HIV序列 从我们的圣地亚哥初级艾滋病毒感染队列（SD PIC）确定参与者之后的时间' 可以快速可靠地推断出传输网络，并且可以利用该网络以更好地度量。 治疗和干预措施的功效，传输风险的相关性以及估计的大小和特征 圣地亚哥艾滋病毒的流行病。拟议的研究还将解决与患者有关的问题 特定的机密性 - 意外披露HIV状态或推定的传播链接。我们将发展 在未来考虑潜在的公共卫生之前，要保留隐私的复杂定量方法 申请。我们的主要假设是HIV预防干预措施的功效，例如TASP（即 ART），可以使用网络统计数据来评估实时时间，可以在特征良好的MSM流行中进行测量 人群中艾滋病毒传播动态的变化。该建议将解决以下具体 目的：1）使用分子流行病学推断圣地亚哥HIV传输网络并使用基于代理 模拟以估计潜在感染人群的特征和潜在干预措施的功效，2） 评估分子流行病学和网络统计数据的潜力，以衡量艺术作为一种 基于网络的预防干预，通过比较发起早期艺术的人的艾滋病毒传播率 与那些延迟或拒绝艺术的人相比，以及3）开发和部署隐私保护方法 用于计算传输网络统计信息。这些相同的方法可以很容易地在潜在的 各种艾滋病毒流行病的时尚，可以帮助优先考虑可用范围 资源。