• Abraham J Kandathil, Florian P Breitwieser, Jaiprasath Sachithanandham, Matthew Robinson, Shruti H Mehta, Winston Timp, Steven L Salzberg, David L Thomas, and Ashwin Balagopal.
• From Johns Hopkins University and Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
• Ann. Intern. Med. 2017 Jul 4; 167 (1): 171-7.

BackgroundNext-generation metagenomic sequencing (NGMS) has opened new frontiers in microbial discovery but has been clinically characterized in only a few settings.ObjectiveTo explore the plasma virome of persons who inject drugs and to characterize the sensitivity and accuracy of NGMS compared with quantitative clinical standards.DesignLongitudinal and cross-sectional studies.SettingA clinical trial (ClinicalTrials.gov: NCT01285050) and a well-characterized cohort study of persons who have injected drugs.ParticipantsPersons co-infected with hepatitis C virus (HCV) and HIV.MeasurementsViral nucleic acid in plasma by NGMS and quantitative polymerase chain reaction (PCR).ResultsNext-generation metagenomic sequencing 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 more than 10 000 copies/mL or IU/mL, respectively, 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. Through use of 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 these persons, 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.LimitationThe medical importance of HHpgV-1 infection is unknown.ConclusionAlthough NGMS is insensitive for detection of viruses with relatively low plasma nucleic acid concentrations, it may have broad potential for discovery of new viral infections of possible medical importance, such as HHpgV-1.Primary Funding SourceNational Institutes of Health.

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