Abraham J. Kandathil, PhD; Florian P. Breitwieser, PhD; Jaiprasath Sachithanandham, PhD; Matthew Robinson, MD; Shruti H. Mehta, PhD; Winston Timp, PhD; Steven L. Salzberg, PhD; David L. Thomas, MD, MPH; Ashwin Balagopal, MD
Grant Support: By the NIH (R01 DA 012568, U01 DA 023832, R01 DA 016078, R37 DA 013806, and R01 HG 006677); the Johns Hopkins University Center for AIDS Research (P30 AI 094189); the Johns Hopkins Institute for Clinical and Translational Research, which is funded in part by grant UL1 TR 000424-06 through a Clinical and Translational Science Award from the National Center for Advancing Translational Sciences, a component of the NIH; the NIH Roadmap for Medical Research; the UJMT Fogarty Global Health Fellows Program (R25 TW 009340); NIH training grant T32 AI 007291; and the U.S. Army Research Office (W911NF-14-1-0490).
Disclosures: Dr. Kandathil reports a grant from the National Institutes of Health before the conduct of the study. Dr. Sachithanandham reports a grant from the National Institutes of Health during the conduct of the study. Dr. Mehta reports grants from the National Institutes of Health during the conduct of the study and outside the submitted work and payment for lectures from Harvard University outside the submitted work. Dr. Thomas reports a grant from the National Institutes of Health and donation of interferon-α from Merck before the conduct of the study. Dr. Balagopal reports a grant from the National Institutes of Health during the conduct of the study. Authors not named here have disclosed no conflicts of interest. Disclosures can also be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M17-0085.
Editors' Disclosures: Christine Laine, MD, MPH, Editor in Chief, reports that she has no financial relationships or interests to disclose. Darren B. Taichman, MD, PhD, Executive Deputy Editor, reports that he has no financial relationships or interests to disclose. Cynthia D. Mulrow, MD, MSc, Senior Deputy Editor, reports that she has no relationships or interests to disclose. Deborah Cotton, MD, MPH, Deputy Editor, reports that she has no financial relationships or interest to disclose. Jaya K. Rao, MD, MHS, Deputy Editor, reports that she has stock holdings/options in Eli Lilly and Pfizer. Sankey V. Williams, MD, Deputy Editor, reports that he has no financial relationships or interests to disclose. Catharine B. Stack, PhD, MS, Deputy Editor for Statistics, reports that she has stock holdings in Pfizer and Johnson & Johnson.
Reproducible Research Statement:Study protocol and data set: Requests for the protocol and data can be sent to Dr. Thomas (e-mail, firstname.lastname@example.org). The HHpgV-1 sequence reported in the manuscript has been deposited in GenBank (GenBank identifier: KY646158). Statistical code: Not applicable.
Requests for Single Reprints: David L. Thomas, MD, MPH, Division of Infectious Diseases, Johns Hopkins School of Medicine, 1830 East Monument Street, Suite 437, Baltimore, MD 21287; e-mail, email@example.com.
Current Author Addresses: Drs. Kandathil and Sachithanandham: Department of Medicine, Johns Hopkins University, 855 North Wolfe Street, #520, Baltimore, MD 21205.
Dr. Breitwieser: Center for Computational Biology, McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University, 1900 East Monument Street, Room 101, Baltimore, MD 21205.
Dr. Robinson: Johns Hopkins Medicine, 600 North Wolfe Street, Phipps 540, Baltimore, MD 21287.
Dr. Mehta: Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, 615 North Wolfe Street, E6546, Baltimore, MD 21231.
Dr. Timp: Department of Biomedical Engineering, Johns Hopkins University, 3400 North Charles Street, Clark 118A, Baltimore, MD 21218.
Dr. Salzberg: Johns Hopkins School of Medicine, Welch Medical Library, Room 107, Baltimore, MD 21205.
Dr. Thomas: Division of Infectious Diseases, Johns Hopkins School of Medicine, 1830 East Monument Street, Suite 437, Baltimore, MD 21287.
Dr. Balagopal: Department of Medicine, Johns Hopkins University, 855 North Wolfe Street, Room 535, Baltimore, MD 21205.
Author Contributions: Conception and design: A.J. Kandathil, F.P. Breitwieser, D.L. Thomas, A. Balagopal.
Analysis and interpretation of the data: A.J. Kandathil, F.P. Breitwieser, M. Robinson, W. Timp, S.L. Salzberg, D.L. Thomas, A. Balagopal.
Drafting of the article: A.J. Kandathil, F.P. Breitwieser, S.L. Salzberg, D.L. Thomas, A. Balagopal.
Critical revision of the article for important intellectual content: A.J. Kandathil, S.H. Mehta, W. Timp, D.L. Thomas, A. Balagopal.
Final approval of the article: A.J. Kandathil, F.P. Breitwieser, J. Sachithanandham, M. Robinson, S.H. Mehta, W. Timp, S.L. Salzberg, D.L. Thomas, A. Balagopal.
Provision of study materials or patients: S.H. Mehta, D.L. Thomas.
Obtaining of funding: S.H. Mehta, S.L. Salzberg, D.L. Thomas, A. Balagopal.
Administrative, technical, or logistic support: W. Timp, A. Balagopal.
Collection and assembly of data: A.J. Kandathil, J. Sachithanandham, W. Timp, D.L. Thomas.
Next-generation metagenomic sequencing (NGMS) has opened new frontiers in microbial discovery but has been clinically characterized in only a few settings.
To explore the plasma virome of persons who inject drugs and to characterize the sensitivity and accuracy of NGMS compared with quantitative clinical standards.
Longitudinal and cross-sectional studies.
A clinical trial (ClinicalTrials.gov: NCT01285050) and a well-characterized cohort study of persons who have injected drugs.
Persons co-infected with hepatitis C virus (HCV) and HIV.
Viral nucleic acid in plasma by NGMS and quantitative polymerase chain reaction (PCR).
Next-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.
The medical importance of HHpgV-1 infection is unknown.
Although 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.
National Institutes of Health.
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Kandathil AJ, Breitwieser FP, Sachithanandham J, Robinson M, Mehta SH, Timp W, et al. Presence of Human Hepegivirus-1 in a Cohort of People Who Inject Drugs. Ann Intern Med. [Epub ahead of print 6 June 2017]:. doi: 10.7326/M17-0085
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Published: Ann Intern Med. 2017.
Gastroenterology/Hepatology, HIV, Infectious Disease, Viral Hepatitis.
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