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

利用血浆病毒组作为注射吸毒者中艾滋病毒风险和传播网络的生物指标

基本信息

批准号：
10700415
负责人：
Steven J. Clipman
金额：
$ 62.48万
依托单位：
JOHNS HOPKINS UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-06-01 至 2028-03-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10700415
关键词：
AIDS prevention Accounting Acquired Immunodeficiency Syndrome Acute Hepatitis C Africa South of the Sahara Baltimore Behavioral Benign Biological Blood Blood specimen Cohort Studies Country County DNA Data Disease Outbreaks Drug usage Epidemic Epidemiology Equipment Event General Population Grant HIV HIV Infections HIV Seropositivity HIV risk HIV/HCV Hepatitis C Hepatitis C Acquisition Hepatitis C Incidence Hepatitis C virus Heroin High Prevalence Human Incidence India Indiana Individual Injecting drug user Injections Interruption Intervention Investigation Legal Link Measures Medical Methods Modeling Molecular Needle Sharing Needle-Exchange Programs Overdose Participant Patient Self-Report Persons Pharmaceutical Preparations Phylogenetic Analysis Plasma Population Population Surveillance Prevalence Prevention Preventive measure Public Health RNA Research Research Personnel Resources Risk Risk Factors Sampling San Francisco Sentinel Social Network Specimen Surveillance Methods System Testing Thailand United States Virus Work case control case finding cohort design disorder control experience high risk injection drug use innovation low and middle-income countries medical complication meetings mortality nanopore new pandemic next generation sequencing novel opioid overdose opioid use predictive tools prescription opioid prevent prevent outbreaks prevention service programs prospective reconstruction response risk prediction rural counties social social stigma substance use success tool transmission process virome

项目摘要

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.

项目概要要实现到 2030 年消除艾滋病这一主要公共卫生威胁的目标，需要覆盖所有人群，特别是那些负担最重的人，例如注射吸毒者（PWID）。注射吸毒者继续经历了全球一些快速增长的艾滋病毒流行。注射吸毒的比例越来越大低收入和中等收入国家以及曾经出现显着下降的国家出现新的艾滋病毒感染病例吸毒者中的艾滋病毒发病率。即使在吸毒者艾滋病毒发病率显着下降的国家，例如在美国，处方阿片类药物使用的增加导致海洛因注射量增加，用药过量率和艾滋病毒爆发。尽管对艾滋病毒的行为驱动因素进行了数十年的调查准确预测谁感染艾滋病毒的风险最高仍然具有挑战性。然而，这些信息对于预防疫情和制定干预措施至关重要。这些工具更在疾病控制、消除或根除计划的最后阶段至关重要，这需要与之前的阶段相比，需要付出更多的努力和资源来识别处于危险中的人，特别是在资源减少和新出现的流行病的背景。当我们迅速接近雄心勃勃的 2030 年目标时，艾滋病毒也是如此，在吸毒者等难以接触到的人群中更是如此，我们需要早期预警系统可指导更有针对性的公共卫生应对措施我们之前证明注射吸毒者在血浆中积累了血源性非致病性病毒丙型肝炎病毒感染。我们还有早期数据显示这些非致病性病毒的序列揭示流行病学联系。本研究以这些发现为基础，探讨吸毒者血浆病毒组是否可以进一步用作艾滋病毒风险的生物指示剂以及是否可以利用它来阻止艾滋病毒的爆发在它们发生之前。为了测试这一点，我们利用了一组罕见的纵向社交（注入伙伴）和空间（注入地点）网络数据以及详细的个人风险因素和高发病率的 HIV 序列印度新德里有超过 2,500 名吸毒者。迄今为止，该队列已观察到超过 159 例 HIV 血清转化。我们计划使用来自参与者的基线样本来表征血浆病毒组后来感染了艾滋病毒，以确定病毒组丰富度是否独立预测艾滋病毒发病率，并评估生物指示剂相对于现有风险预测工具的附加值。此外，我们计划排序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部和宿主之间传播的非致病性病毒的多样性，以利用系统发育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，这项工作可能会产生更强大的分子监测方法，可以指导公共卫生官员采取有针对性的干预措施，以预防艾滋病毒爆发并集中有限的资源以获得最大的影响。