Dynamics of viremia in early hepatitis C virus infection

Authors

  • Simone A. Glynn,

    1. From Westat, Rockville, Maryland; the University of British Columbia, Victoria, British Columbia, Canada; the Blood Centers of the Pacific, San Francisco, California; Alpha Therapeutic Corporation, Los Angeles, California; the National Genetics Institute, Los Angeles, California; Gen-Probe Inc., San Diego, California; Roche Molecular Systems, Pleasanton, California; and the University of California, San Francisco, California.
    Search for more papers by this author
  • David J. Wright,

    1. From Westat, Rockville, Maryland; the University of British Columbia, Victoria, British Columbia, Canada; the Blood Centers of the Pacific, San Francisco, California; Alpha Therapeutic Corporation, Los Angeles, California; the National Genetics Institute, Los Angeles, California; Gen-Probe Inc., San Diego, California; Roche Molecular Systems, Pleasanton, California; and the University of California, San Francisco, California.
    Search for more papers by this author
  • Steven H. Kleinman,

    1. From Westat, Rockville, Maryland; the University of British Columbia, Victoria, British Columbia, Canada; the Blood Centers of the Pacific, San Francisco, California; Alpha Therapeutic Corporation, Los Angeles, California; the National Genetics Institute, Los Angeles, California; Gen-Probe Inc., San Diego, California; Roche Molecular Systems, Pleasanton, California; and the University of California, San Francisco, California.
    Search for more papers by this author
  • Dale Hirschkorn,

    1. From Westat, Rockville, Maryland; the University of British Columbia, Victoria, British Columbia, Canada; the Blood Centers of the Pacific, San Francisco, California; Alpha Therapeutic Corporation, Los Angeles, California; the National Genetics Institute, Los Angeles, California; Gen-Probe Inc., San Diego, California; Roche Molecular Systems, Pleasanton, California; and the University of California, San Francisco, California.
    Search for more papers by this author
  • Yongling Tu,

    1. From Westat, Rockville, Maryland; the University of British Columbia, Victoria, British Columbia, Canada; the Blood Centers of the Pacific, San Francisco, California; Alpha Therapeutic Corporation, Los Angeles, California; the National Genetics Institute, Los Angeles, California; Gen-Probe Inc., San Diego, California; Roche Molecular Systems, Pleasanton, California; and the University of California, San Francisco, California.
    Search for more papers by this author
  • Charles Heldebrant,

    1. From Westat, Rockville, Maryland; the University of British Columbia, Victoria, British Columbia, Canada; the Blood Centers of the Pacific, San Francisco, California; Alpha Therapeutic Corporation, Los Angeles, California; the National Genetics Institute, Los Angeles, California; Gen-Probe Inc., San Diego, California; Roche Molecular Systems, Pleasanton, California; and the University of California, San Francisco, California.
    Search for more papers by this author
  • Richard Smith,

    1. From Westat, Rockville, Maryland; the University of British Columbia, Victoria, British Columbia, Canada; the Blood Centers of the Pacific, San Francisco, California; Alpha Therapeutic Corporation, Los Angeles, California; the National Genetics Institute, Los Angeles, California; Gen-Probe Inc., San Diego, California; Roche Molecular Systems, Pleasanton, California; and the University of California, San Francisco, California.
    Search for more papers by this author
  • Cristina Giachetti,

    1. From Westat, Rockville, Maryland; the University of British Columbia, Victoria, British Columbia, Canada; the Blood Centers of the Pacific, San Francisco, California; Alpha Therapeutic Corporation, Los Angeles, California; the National Genetics Institute, Los Angeles, California; Gen-Probe Inc., San Diego, California; Roche Molecular Systems, Pleasanton, California; and the University of California, San Francisco, California.
    Search for more papers by this author
  • James Gallarda,

    1. From Westat, Rockville, Maryland; the University of British Columbia, Victoria, British Columbia, Canada; the Blood Centers of the Pacific, San Francisco, California; Alpha Therapeutic Corporation, Los Angeles, California; the National Genetics Institute, Los Angeles, California; Gen-Probe Inc., San Diego, California; Roche Molecular Systems, Pleasanton, California; and the University of California, San Francisco, California.
    Search for more papers by this author
  • Michael P. Busch

    Corresponding author
    1. From Westat, Rockville, Maryland; the University of British Columbia, Victoria, British Columbia, Canada; the Blood Centers of the Pacific, San Francisco, California; Alpha Therapeutic Corporation, Los Angeles, California; the National Genetics Institute, Los Angeles, California; Gen-Probe Inc., San Diego, California; Roche Molecular Systems, Pleasanton, California; and the University of California, San Francisco, California.
    Search for more papers by this author

  • This work was supported by the National Heart, Lung and Blood Institute Contracts N01-HB-97077 (superseded by N01-HB-47114), -97078, -97079, -97080, -97081, and -97082 through the Retrovirus Epidemiology Donor Study. Data on plasma donor panels were provided by the Alpha Therapeutic Corporation and the National Genetics Institute and testing reagents by the manufacturers of the NAT assay systems (Roche Molecular Systems and Gen-Probe, Inc.).

Michael P. Busch, MD, PhD, Blood Systems Research Institute, 270 Masonic Avenue, San Francisco, CA 94118; e-mail: mpbusch@itsa.ucsf.edu.

Abstract

BACKGROUND: It is important to characterize viral dynamics in early hepatitis C virus (HCV) infection to further our understanding of viral pathogenesis and the potential for secondary transmission in acute infection through blood transfusion or other routes.

STUDY DESIGN AND METHODS: Serial units given by 77 source plasma donors who had evolved from HCV RNA–negative to HCV RNA–positive by nucleic acid amplification technology (NAT) screening with 512-unit pool-NAT or were followed from RNA detection to antibody conversion were tested by individual NAT and quantitative RNA assays.

RESULTS: During the ramp-up phase when exponential growth occurs, HCV viral load doubled every 10.8 hours (95% confidence interval [CI], 9.9-12.0). Intermittent viremia was observed before the ramp-up phase in 37 of 50 panels with the earliest detectable viremic bleed occurring 63 days before the estimated onset of ramp-up. The plateau phase or high-titer viremic period that occurs between ramp-up and seroconversion was estimated to last 56.3 days (95% CI, 44.8-67.8).

CONCLUSIONS: Intermittent low-level HCV viremia can occur as much as 2 months before the periods of exponential increase in viral load and the high-titer plateau-phase viremia that usually precede seroconversion. Animal inoculation studies are in progress to evaluate if transfusion of low-level viremic plasma can transmit HCV infection.

Ancillary