Characterization of plasma virome in people who inject drugs to identify early transmission networks of HIV and other bloodborne infections

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There is an urgent need for implementing innovative methods to combat the resurgence of HIV and hepatitis C virus (HCV) infection among people who inject drugs (PWID). The opioid epidemic in the United States threatens to undermine national 2030 elimination goals for both viruses. While tertiary prevention strategies have facilitated to a certain extent in improving health outcomes it has been difficult to interdict transmission of infectious diseases. Moreover, bloodborne infections like HIV and HCV have no symptoms on initial infection, and thus the beginning of an epidemic can predate the recognition of the first diagnosed case in the community. In addition, surveillance is also hindered by disincentives for “self-report” caused by stigmatization and criminalization. We propose using plasma virome components shared between subjects due to intravenous injection of illicit drugs for early identification of transmission networks in PWID. Transmission studies have shown that HCV precedes HIV infection in PWID, and hence new HCV infections serve as strong predictors of communities at risk for HIV. We now ask if there are virome components that are shared before HCV transmission in PWID. Our hypothesis is that viruses of unknown pathogenicity will accumulate in blood before HIV or HCV infection and that they will be transmitted by injection drug use such that their sequences reveal those epidemiological linkages. We will first confirm our preliminary observations made in our Baltimore cohort using molecular and serology assessments in another PWID cohort from San Francisco. Like the Baltimore cohort, the San Francisco cohort allows access to plasma samples before, during, and after acquisition of HCV infection. We will compare plasma virome between age and gender matched twenty HCV positive (HCV+PWID) and twenty HCV negative (HCV-PWID) PWID. Plasma from two time points covering the same duration of follow up between the two groups will be tested. The HCV+PWID will be tested before and during acquisition of HCV. Differences will be determined by enumerating viral infections between the groups at both time points. The plasma virome will then be characterized further by NGS using Oxford Nanopore after viral target enrichment. The long reads allow identification of viral strains (haplotype) suitable for phylogenetic studies. We will characterize the plasma virome in subjects from the Baltimore cohort (n=10) known to share (linked) HCV sequences. In addition, we will sequence the same subjects before HCV acquisition to identify shared (linked) virome sequences before HCV acquisition. Similar sequence characterization of plasma samples from the San Francisco cohort (n=10) will also be done at two time points. Sequencing both cohorts further validates the approach since no sequence sharing (linkage) of the virome components should be observed between the two cohorts. By using routinely collected samples, this work could transform the research of drug use networks and change public health surveillance of HIV, HCV, and expose occult dynamics of reinfection and superinfection.