Efficacy of ART to Interrupt HIV Transmission Networks

描述（由申请人提供）：抗逆转录病毒治疗（ART）显着降低了稳定的艾滋病毒不和谐的异性伴侣之间的艾滋病毒传播的风险，增加ART的使用可以影响艾滋病毒发病率的“人口水平”降低。艾滋病毒预防干预措施，如ART“治疗即预防”（TasP）战略是否可以显著降低流行病的增长率仍然是一个相当大的争论问题，尽管目前的社区随机TasP试验将需要大量的基础设施和财政资源。需要采取其他的、资源限制较少的办法，理想的是，这些办法还能实时了解艾滋病毒的传播动态，并易于修改，以解决独特的区域和流行病学因素。针对艾滋病毒传播流行病学“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机会。有效的预防干预措施对男男性行为人群特别重要，因为与其他风险群体相比，他们的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来估计真实的时间在新的艾滋病毒诊断的人向前传播艾滋病毒的风险。我们已经证明，通过评估从我们的圣地亚哥初级艾滋病毒感染队列（SD PIC）中识别出参与者后“真实的-时间”生成的艾滋病毒序列，可以快速可靠地推断出部分传播网络，并且可以利用该网络更好地测量治疗和干预措施的有效性，传播风险的相关性，并估计圣地亚哥艾滋病毒流行病的规模和特征。拟议的研究还将解决与患者保密性有关的问题，特别是无意中披露艾滋病毒状态或假定的传播联系。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之前保护隐私。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），可以在一个特征明确的MSM流行病中进行测量，使用网络统计数据来评估人群中艾滋病毒传播动态的真实的时间变化。该提案将针对以下具体目标：1）使用分子流行病学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感染人群的特征和潜在干预措施的有效性，2）评估分子流行病学和网络统计的潜力，以衡量ART作为基于网络的预防干预措施的有效性，通过比较早期开始ART的人与延迟或拒绝ART的人的HIV传播率，以及3）开发和部署用于计算传播网络统计的隐私保护方法。同样的方法可以很容易地在各种艾滋病毒流行病中以前瞻性的方式推广，并有助于在现有资源范围内确定干预措施的优先次序。

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.