Efficacy of ART to Interrupt HIV Transmission Networks

抗逆转录病毒治疗（ART）显着降低了稳定的艾滋病毒不一致之间的艾滋病毒传播风险 异性伴侣和增加抗逆转录病毒疗法的使用可以影响“人口一级”艾滋病毒发病率的降低。 艾滋病毒预防干预措施，如ART“治疗即预防”战略， 大幅度降低流行病增长率仍然是一个相当有争议问题， 社区随机TasP试验将需要大量的基础设施和财政资源。替代方案中小于 需要一种资源有限的方法，理想情况下，这种方法还可以提供对艾滋病毒的实时了解 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 艾滋病毒的传播可能为有效中断艾滋病毒传播链提供机会。有效预防 干预措施对男男性行为者（MSM）人群尤其重要，因为他们 与其他风险群体相比，发病率高得不成比例。我们建议使用分子 流行病学和计算建模，以真实的时间估计艾滋病毒传播的风险， 新诊断出艾滋病毒的人。我们已经证明，通过评估在“真实的”中产生的HIV序列， 在从我们的圣地亚哥原发性HIV感染队列（SD PIC）中确定参与者后， 可以快速可靠地推断出传输网络，并且可以利用该网络来更好地测量 治疗和干预措施的有效性，传播风险的相关性，以及估计规模和特征 圣地亚哥艾滋病病毒的流行。拟议的研究还将解决与患者相关的问题。 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， 应用.我们的主要假设是，艾滋病毒预防干预措施的有效性，如TasP（即， ART），可以在一个特征良好的MSM流行病中测量，使用网络统计来评估真实的时间 人口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）利用分子流行病学方法推断圣地亚哥HIV传播网络，并使用基于代理的 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学的潜力，以衡量ART作为一种治疗方法的疗效。 基于网络的预防干预，通过比较早期开始抗逆转录病毒治疗者的艾滋病毒传播率 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。同样的方法可以很容易地在前瞻性研究中复制。 在不同的艾滋病毒流行病中流行，并有助于在现有的范围内优先考虑干预措施。 资源

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.