Efficacy of ART to Interrupt HIV Transmission Networks

ART 阻断 HIV 传播网络的功效

• 批准号: 8848139
• 负责人: SUSAN JANET LITTLE
• 金额: $ 64.79万
• 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/8848139
• 关键词: AIDS prevention; Address; Affect; Alcohol or Other Drugs use; Anti-Retroviral Agents; Calibration; Cluster randomized trial; 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; Health; Heterosexuals; Hot Spot; Incidence; Individual; Infection; Information Networks; Intervention; Link; Measures; Methods; Molecular Epidemiology; Nature; Network-based; Participant; Persons; Population; Prevention; Prevention strategy; Prevention trial; 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; reproductive; simulation; statistics; theories; transmission process; virus genetics

DESCRIPTION (provided by applicant): 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 ar 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.

描述（由申请人提供）：抗逆转录病毒治疗（ART）显着降低了稳定的HIV不和谐异性伴侣和不断增加的ART使用之间的HIV传播风险，可以影响HIV发病率的“人口级”减少。尽管当前的社区随机TASP试验将需要大量的基础设施和财务资源，但诸如“预防疗法”（TASP）策略（TASP）策略等艾滋病毒预防干预措施是否可以显着降低流行病的增长率。需要采用替代性，较少的资源过度方法，理想情况下，这也将提供对HIV传播动态的实时见解，并易于修改以解决独特的区域和流行病学因素。针对艾滋病毒传播的流行病学“热点”的预防和治疗干预措施的前瞻性研究可能为有效中断艾滋病毒传播链提供了机会。有效的预防干预措施与与其他风险群体相比，与男性发生性关系（MSM）的男人（MSM）特别相关。我们建议使用分子流行病学和计算模型实时估算新艾滋病毒诊断的人的艾滋病毒传播风险。 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.拟议的研究还将解决与患者机密性有关的问题，尤其是 - 艾滋病毒状况的意外披露或推定的传播链接，我们将开发复杂的定量方法，以在未来考虑潜在的公共卫生应用程序之前保留隐私。我们的主要假设是，可以使用网络统计数据来评估人群中HIV传播动态的实时变化，可以在良好的特征MSM流行中测量HIV预防干预措施（例如TASP（即ART））的疗效。该提议将解决以下特定目的：1）使用分子流行病学来推断圣地亚哥艾滋病毒传播网络，并使用基于代理的模拟来估计潜在的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在，以衡量基于网络的动作率，以与网络统计的效率相比，以与网络的效率进行比较，以相比，该人的预期率是在预期的效率上，以相比，以比较HY衰落的艺术，3）开发和部署隐私保留用于计算传输网络统计的方法。这些相同的方法很容易以在各种艾滋病毒流行病的方式中的潜在方式复制，并有助于在可用资源范围内优先考虑干预措施。