Leveraging the plasma virome as a biological indicator of HIV risk and transmission networks among people who inject drugs

项目摘要 要实现到2030年消除艾滋病这一主要公共卫生威胁的目标，就需要惠及所有人口， 特别是那些负担最重的人，如注射毒品的人。PWID继续 在全球范围内，艾滋病毒的流行正在迅速蔓延。注射毒品越来越多地占 在低收入和中等收入国家以及艾滋病毒感染率曾显著下降的国家， 艾滋病毒感染者的发病率。即使在艾滋病毒感染者发病率显著下降的国家， 在美国，处方阿片类药物使用的增加导致海洛因注射增加， 吸毒过量和艾滋病爆发尽管对艾滋病毒的行为驱动因素进行了数十年的调查， 尽管艾滋病毒/艾滋病发病率很高，但准确预测谁感染艾滋病毒的风险最高仍然是一项挑战。 然而，这些信息对于预防疫情和调整干预措施至关重要。这些工具甚至更多 在疾病控制、消除或根除计划的最后阶段至关重要， 与前几个阶段相比，为查明处于危险中的人，特别是在 资源日益减少和流行病不断出现的背景。随着我们迅速接近雄心勃勃的2030年目标， 艾滋病毒也是如此，在难以接触到的人群中，如艾滋病患者，情况更是如此，我们需要 早期预警系统，以指导更有针对性的公共卫生应对措施 我们以前证明，PWID积累血液传播的非致病性病毒在血浆中之前， 丙型肝炎病毒感染我们也有早期数据显示这些非致病性病毒的序列 揭示流行病学的联系本研究在这些发现的基础上探讨PWID中的血浆病毒组是否 可进一步用作艾滋病毒风险的生物指示剂，以及是否可利用它来中断艾滋病毒爆发 在它们发生之前。为了验证这一点，我们利用了一组罕见的纵向社会（注入伙伴）和空间（注入 地点）网络数据沿着详细的个人层面的风险因素和艾滋病毒序列，从一个高发病率 印度新德里的2,500多名残疾人。迄今为止，该队列已观察到超过159例艾滋病毒感染者， 血清转化我们计划使用来自参与者的基线标本来表征血浆病毒组， 以确定病毒组丰富度是否独立预测HIV发病率，并评估 生物指示剂相对于现有风险预测工具的附加值。另外，我们计划 参与者组成完整的联系网络，并利用下一代测序方法， 捕获宿主内和宿主间传播的非致病性病毒的多样性， 旨在确定血浆病毒组序列是否可以准确推断传播网络的方法。 通过使用常规收集的样本，这项工作可能会导致更强大的分子监测方法， 可以指导公共卫生官员有针对性地采取干预措施，防止艾滋病毒爆发，并集中有限的资源 最大的影响。

PROJECT SUMMARY Meeting targets set to end AIDS as a major public health threat by 2030 requires reaching all populations, particularly those with the highest burden, such as people who inject drugs (PWID). PWID continue to experience some of the fast-growing HIV epidemics globally. Injection drug use is increasingly accounting for new HIV infections in both low- and middle-income countries and countries that once saw notable declines in HIV incidence among PWID. Even in countries with notable declines in HIV incidence among PWID, such as the United States, the rise of prescription opioid use has resulted in increased heroin injection, increased overdose rates, and outbreaks of HIV. Despite decades of investigation into the behavioral drivers of HIV incidence, accurately predicting who is at the highest risk of becoming infected with HIV remains challenging. Yet, this information is critical for preventing outbreaks and tailoring interventions. These tools are even more critical at the final stages of disease control, elimination, or eradication programs which require disproportionately more effort and resources than in preceding stages to identify those at risk, especially in a setting of dwindling resources and emerging pandemics. As we rapidly approach the ambitious 2030 targets, the same will be true of HIV, even more so among hard-to-reach populations such as PWID, and we need early warning systems to guide a more targeted public health response We previously demonstrated that PWID accumulate blood-borne nonpathogenic viruses in the plasma before hepatitis C virus infection. We also have early data showing that sequences of these nonpathogenic viruses reveal epidemiologic links. This study builds on these findings to explore whether the plasma virome in PWID can be further used as a bioindicator of HIV risk and whether it can be leveraged to interrupt HIV outbreaks before they occur. To test this, we utilize a rare set of longitudinal social (injection partner) and spatial (injection venue) network data along with detailed individual-level risk factors and HIV sequences from a high-incidence cohort of over 2,500 PWID in New Delhi, India. To date, this cohort has observed over 159 HIV seroconversions. We plan to characterize the plasma virome using baseline specimens from participants who later acquired HIV to determine if virome richness independently predicts HIV incidence and to assess the added value of a bioindicator over established risk prediction tools. Additionally, we plan to sequence participants comprising complete contact networks and leverage next-generation sequencing approaches that capture the diversity of nonpathogenic viruses circulating within and between hosts to employ phylogenetic methods aimed at determining whether plasma virome sequences can accurately infer transmission networks. By using routinely collected samples, this work could lead to more robust molecular surveillance methods that can guide public health officials in targeting interventions to prevent HIV outbreaks and focus limited resources for the greatest impact.