Public health targeting of PrEP at HIV positives' bridging networks

 描述(由申请人提供)：这项发展研究补助金(R21)要求提供资金，以探索公共卫生系统PrEP干预最近在希腊雅典出现的艾滋病毒流行的可行性和影响。由于全球大多数环境中的艾滋病毒流行已趋于稳定或正在下降，新出现的流行病、重新出现的流行病或暴发将变得更加常见，特别是当影响艾滋病毒预防资源的社会、政治或其他“冲击”发生时。一个典型的例子是最近在注射毒品者中流行的(PWID)，这种流行病始于雅典，始于2010年的紧缩措施。虽然观察到在PWID内控制疫情方面取得了一些成功，但最近的系统发育和监测分析表明，最近一次PWID疫情(CRF35_AD、CRF14_BG，A和B亚型)的艾滋病毒毒株已在2013年蔓延到MSM(见初步研究)。在新出现的流行病中，口服化学预防是预防易感人群感染疾病的常用公共卫生策略。例如，在美国和欧洲的MSM中，在侵袭性脑膜炎双球菌疾病暴发中为性伴侣提供抗生素预防的情况有限。同样，暴露前预防(PrEP)有可能用于新出现的流行病，以防止艾滋病毒的进一步传播。虽然这种方法看起来很直观，但目前对PrEP实施的概念化仅使用了专注于卫生服务提供者和客户之间的个性化干预的临床模型。这是有问题的，因为由于缺乏适当的目标，PrEP对公共卫生的影响可能有限。事实上，来自“真实世界”PrEP使用的证据表明，较低风险的客户正在访问PrEP。与资源密集型临床试验或示范研究相比，仔细的建模方法可以提供洞察，了解在新的艾滋病毒流行中，谁应该成为PrEP的目标，以防止进一步传播，以及用于识别这些人并将他们与护理联系起来的策略。我们提出了一种使用基于代理的模型(ABM)的建模方法，该模型超越了基本的病原体和传播模式，转向处理复杂的社会交互，包括重叠的社会和性网络以及实施现实，如有限的PrEP资源、与PrEP护理的延迟联系以及基于希腊雅典经验收集的数据的早期准备护理保留。具体地说，我们的目标是：1)通过测量个体水平的风险因素、网络水平的联系和艾滋病毒系统发生簇来表征桥接的MSM网络(n=250)；2)测量短期内未感染HIV的MSM的一个子样本(n=50)的早期PrEP级联结果(HIV检测、PrEP与护理的联系)；以及3)模拟这种有针对性的公共卫生PrEP干预对雅典HIV传播的影响。解释经验性网络结构的基于代理人的模型在模拟艾滋病毒传播方面是最先进的，并且足够灵活，可以解决谁应该接受PrEP以及最终网络PrEP干预如何影响新出现的/重新出现的HIV流行病的基本问题。

 DESCRIPTION (provided by applicant): This developmental research grant award (R21) requests funds to explore the feasibility and impact of a public health system PrEP intervention in a recently emerging HIV epidemic in Athens Greece. As HIV epidemics in most settings globally have plateaued or are in decline, emerging epidemics, re-emerging epidemics or outbreaks will become more common, particularly when social, political or other "shocks" that impact HIV prevention resources occur. One well characterized example is the recent epidemic among people who inject drugs (PWID) that started in Athens following austerity measures in 2010. While some success in limiting the epidemic within PWID has been observed, recent phylogenetic and surveillance analysis demonstrates that the HIV strain from this most recent PWID epidemic (CRF35_AD, CRF14_BG, subtypes A and B) has spilled over into MSM in 2013 (see Preliminary Studies). In emerging epidemics, oral chemoprophylaxis is a commonly-used public health strategy to prevent infectious diseases in susceptible persons. For example, among US and European MSM, antibiotic prophylaxis for sex-partners in outbreaks of invasive meningococcal disease has limited emerging outbreaks. Similarly, pre-exposure prophylaxis (PrEP) has the potential to be used in emerging epidemics to prevent onwards HIV transmission. While this approach would seem intuitive, current conceptualizations of PrEP implementation narrowly use a clinical model focused on individualized intervention between health provider and client. This is problematic because the public health impact of PrEP may be limited due to lack of proper targeting. In fact, evidence from "real-world" PrEP use suggests that lower risk clients are accessing PrEP. As compared to resource intensive clinical trials or demonstration studies, careful modeling approaches can provide insight into who within a new HIV epidemic should be targeted for PrEP to prevent onward transmission as well as the strategies used to identify these individuals and link them to care. We propose a modeling approach using an Agent Based Model (ABM) that moves beyond basic pathogen and transmission patterns to dealing with complex social interactions, including overlapping social and sexual networks as well as implementation realities, like finite PrEP resources, delayed linkage to PrEP care and early PreP care retention based upon empirically collected data in Athens Greece. Specifically we aim to: 1) Characterize a bridging MSM network (n=250) by measuring individual-level risk factors, network-level connections, and HIV phylogenetic clusters; 2) Measure early PrEP cascade outcomes (HIV testing, PrEP linkage to care) of a sub-sample (n=50) of HIV uninfected MSM over the short term; and 3) Model the effects of this targeted public health PrEP intervention on HIV transmission in Athens. Agent-based models that account for empirical network structure are state-of- the-art in modeling HIV transmission and are flexible enough to address fundamental questions of who should receive PrEP and ultimately how a network-PrEP intervention can impact emerging/reemerging HIV epidemics.