Efficacy of ART to Interrupt HIV Transmission Networks

描述(由申请人提供)：抗逆转录病毒疗法(ART)显著降低了艾滋病毒在稳定的、不和谐的异性伴侣之间传播的风险，增加抗逆转录病毒疗法的使用可以有效地降低艾滋病毒发病率的“人群水平”。艾滋病毒预防干预措施，如抗逆转录病毒治疗和预防(TasP)战略是否能够显著降低流行病增长率仍是一个相当有争议的问题，尽管目前社区随机TasP试验将需要大量的基础设施和财政资源。需要替代的、资源禁止性较低的方法，理想情况下，这种方法还将提供对艾滋病毒传播动态的实时洞察，并易于修改以解决独特的区域和流行病因素。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男男性行为者(MSM)人群中尤其相关，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模型来实时估计在新诊断的HIV患者中继续传播HIV的风险。我们已经证明，通过评估从我们的圣地亚哥主要艾滋病毒感染队列(SD PIC)中确定参与者后实时产生的艾滋病毒序列，可以快速而可靠地推断出部分传播网络，并且可以利用该网络更好地衡量治疗和干预的效果、传播风险的相关性，以及估计圣地亚哥艾滋病毒流行的规模和特征。拟议的研究还将解决与患者保密有关的问题，特别是意外披露艾滋病毒状况或假定的传播链接。在未来考虑潜在的公共卫生应用之前，我们将开发复杂的量化方法来保护隐私。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)，可以在具有良好特征的男男性接触者流行中衡量，使用网络统计来评估人群中艾滋病毒传播动态的实时变化。这项建议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，并使用基于试剂的模拟来评估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学的潜力，通过比较早期启动抗逆转录病毒疗法的人与推迟或拒绝抗逆转录病毒疗法的人的艾滋病毒传播率，来衡量抗逆转录病毒疗法作为基于网络的预防干预的有效性；以及3)开发和部署用于计算传输网络统计数据的隐私保护方法。这些同样的方法可以很容易地在不同的艾滋病毒流行中以前瞻性的方式复制，并有助于在现有资源范围内确定干预措施的优先顺序。

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.