Efficacy of ART to Interrupt HIV Transmission Networks

ART 阻断 HIV 传播网络的功效

基本信息

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
项目类别：
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

项目摘要

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) 显着降低稳定的 HIV 不一致者之间传播 HIV 的风险异性伴侣和增加抗逆转录病毒治疗的使用可以实现“人口水平”艾滋病毒发病率的降低。 HIV 预防干预措施（例如 ART“治疗即预防”（TasP）策略）是否可以显着降低流行病增长率仍然是一个颇有争议的问题，尽管目前社区随机 TasP 试验需要大量的基础设施和财政资源。另类，少需要资源限制方法，理想情况下也能提供对艾滋病毒的实时洞察传播动态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提供有效中断艾滋病毒传播链的机会。有效预防干预措施对于男男性行为者 (MSM) 人群尤其重要，因为他们与其他危险人群相比，发病率高得不成比例。我们建议使用分子流行病学和计算模型实时估计艾滋病毒继续传播的风险新诊断出艾滋病毒的人。我们已经证明，通过评估“真实”中生成的 HIV 序列，在我们的圣地亚哥原发性 HIV 感染队列 (SD PIC) 中确定了一名参与者后，部分参与者可以快速可靠地推断传输网络，并且可以利用该网络更好地测量治疗和干预措施的功效、传播风险的相关性，并估计病毒的大小和特征圣地亚哥艾滋病毒流行情况。拟议的研究还将解决与患者相关的担忧保密性，特别是 - 无意中披露艾滋病毒状况或假定的传播联系。我们将开发在未来考虑潜在的公共健康之前保护隐私的复杂定量方法应用程序。我们的主要假设是 HIV 预防干预措施的有效性，例如 TasP（即 ART），可以在明确描述的 MSM 流行病中进行测量，使用网络统计数据来实时评估人群中艾滋病毒传播动态的变化。该提案将解决以下具体问题目的： 1) 使用分子流行病学和基于媒介的方法推断圣地亚哥 HIV 传播网络通过模拟来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在衡量 ART 作为一种治疗手段的功效方面的潜力基于网络的预防干预，通过比较开始早期抗逆转录病毒治疗的人的艾滋病毒传播率与那些延迟或拒绝 ART 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数据。这些相同的方法可以很容易地在未来的应用中复制流行于各种艾滋病毒流行病中，并有助于在现有范围内确定干预措施的优先顺序资源。