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

• 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
• 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

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.

项目摘要 到2030年，达到最终艾滋病的目标目标是达到所有人口的主要公共卫生威胁， 特别是那些负担最高的人，例如注入毒品的人（PWID）。 PWID继续 在全球范围内体验一些快速增长的艾滋病毒流行病。注射毒品使用越来越多地考虑 低收入和中等收入国家和曾经显着下降的国家的新艾滋病毒感染 PWID之间的艾滋病毒发病率。即使在PWID中艾滋病毒发病率下降的国家，例如 美国，处方阿片类药物使用的兴起导致海洛因注射增加，增加 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 发病率，准确地预测谁受到艾滋病毒感染的风险最高仍然具有挑战性。 但是，此信息对于防止爆发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，需要 比以前的阶段要识别有风险的人，尤其是在一个阶段，尤其是在 设置减少资源和新兴大流行。当我们迅速接近雄心勃勃的2030个目标时， 艾滋病毒也是如此，在诸如PWID之类的难以到达的人群中也是如此，我们需要 预警系统指导更有针对性的公共卫生反应 我们先前证明了PWID之前在血浆中积累了血液传播的非对病毒病毒 丙型肝炎病毒感染。我们还拥有早期数据，显示了这些非致病病毒的序列 揭示流行病学链接。这项研究以这些发现为基础，以探索PWID中的等离子体病毒蛋白 可以进一步用作艾滋病毒风险的生物指导者，以及是否可以利用它来中断艾滋病毒爆发 在发生之前。为了测试这一点，我们利用一组罕见的纵向社会（注射伙伴）和空间（注射 网站）网络数据以及高累积的详细个人级别风险因素和HIV序列 印度新德里的2500多个PWID的队列。迄今为止，该队列已经观察到超过159 HIV 血清转化。我们计划使用参与者的基线标本来表征血浆病毒蛋白 后来获得了HIV，以确定病毒蛋白丰富度是否独立预测了HIV的发病率并评估 生物指导者的附加值比已建立的风险预测工具。此外，我们计划对 包括完整的联系网络并利用下一代测序方法的参与者 捕获在宿主内部和宿主之间循环的非致病病毒的多样性，以采用系统发育 旨在确定血浆病毒蛋白序列是否可以准确推断传输网络的方法。 通过使用常规收集的样品，这项工作可能导致更健壮的分子监视方法， 可以指导公共卫生官员针对干预措施，以防止艾滋病毒爆发并集中于有限的资源 最大的影响。