4.8 Article

Modeling of patient virus titers suggests that availability of a vaccine could reduce hepatitis C virus transmission among injecting drug users

Journal

SCIENCE TRANSLATIONAL MEDICINE
Volume 10, Issue 449, Pages -

Publisher

AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/scitranslmed.aao4496

Keywords

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Funding

  1. FDA intramural funds [Z01 BK 04010-11]
  2. NIH [R01-AI078881, 1R01-GM121600-01A1]
  3. Victorian Operational Infrastructure Support Program
  4. CBER/FDA
  5. Australian National Health and Medical Research Council Early Career Fellowships
  6. NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [R01AI078881] Funding Source: NIH RePORTER
  7. NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [R01GM121600] Funding Source: NIH RePORTER
  8. NATIONAL INSTITUTE ON DRUG ABUSE [R01DA043484] Funding Source: NIH RePORTER

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The major route of hepatitis C virus (HCV) transmission in the United States is injection drug use. We hypothesized that if an HCV vaccine were available, vaccination could affect HCV transmission among people who inject drugs by reducing HCV titers after viral exposure without necessarily achieving sterilizing immunity. To investigate this possibility, we developed a mathematical model to determine transmission probabilities relative to the HCV RNA titers of needle/syringe-sharing donors. We simulated sharing of two types of syringes fitted with needles that retain either large or small amounts of fluid after expulsion. Using previously published viral kinetics data from both naive subjects infected with HCV and reinfected individuals who had previously cleared an HCV infection, we estimated transmission risk between pairs of serodiscordant injecting drug users, accounting for syringe type, rinsing, and sharing frequency. We calculated that the risk of HCV transmission through syringe sharing increased similar to 10-fold as viral titers (log(10) IU/ml) increased similar to 25-fold. Cumulative analyses showed that, assuming sharing episodes every 7 days, the mean transmission risk over the first 6 months was >90% between two people sharing syringes when one had an HCV RNA titer >5 log(10) IU/ml. For those with preexisting immunity that rapidly controlled HCV, the cumulative risk decreased to 1 to 25% depending on HCV titer and syringe type. Our modeling approach demonstrates that, even with transient viral replication after exposure during injection drug use, HCV transmission among people sharing syringes could be reduced through vaccination if an HCV vaccine were available.

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