Background
Next-generation metagenomic sequencing (NGMS) has opened new frontiers in microbial discovery but has been clinically characterized in only a few settings.
Objective
To explore the plasma virome of persons who inject drugs while characterizing the sensitivity and accuracy of NGMS compared to quantitative clinical standards.
Design
Longitudinal and cross-sectional studies.
Participants
Hepatitis C virus (HCV) and human immunodeficiency virus (HIV) co-infected persons enrolled in a clinical trial (NCT01285050) and/or a well-characterized cohort study of persons who have injected drugs.
Measurements
Viral nucleic acid in plasma by NGMS and quantitative polymerase chain reaction (PCR).
Results
NGMS generated a total of 600 million reads, which included the expected HIV and HCV RNA sequences. HIV and HCV reads were consistently identified only when samples contained >10,000 copies or IU/ml as determined by quantitative PCR. A novel RNA virus, human hepegivirus-1 (HHpgV-1) was also detected by NGMS in 4 samples from 2 persons in the clinical trial. Because of this unexpected finding, using a quantitative PCR assay for HHpgV-1, infection was also detected in 17 (10.9%) of 156 members of a cohort of persons who injected drugs in whom HHpgV-1 viremia persisted for a median of at least 4538 days and was associated with detection of other bloodborne viruses such as HCV RNA and SEN virus D
Limitations
The medical importance of HHpgV-1infection remains unknown.
Conclusions
Although NGMS is insensitive to detection of viruses with relatively low plasma nucleic acid concentrations, it may have a broad potential for discovery of new viral infections of potential medical importance like HHpgV-1.