Abstract

BACKGROUND: We aimed to characterize the natural history of hepatitis C virus (HCV) reinfection and spontaneous clearance following reinfection (reclearance), including predictors of HCV reclearance. METHODS: Data were synthesised from nine prospective cohorts evaluating HCV infection outcomes among people who inject drugs (InC3 study). Participants with primary HCV infection were classified as achieving viral suppression if they had at least one subsequent negative HCV RNA test. Those with a positive HCV RNA test following viral suppression were investigated for reinfection. Viral sequence analysis was used to identify reinfection (heterologous virus with no subsequent detection of the original viral strain). RESULTS: Among 591 participants with acute primary HCV infection, 118 were investigated for reinfection. Twenty-eight participants were reinfected (12.3/100 person-years, 95%CI: 8.5-17.8). Peak HCV RNA was lower in reinfection than primary infection (p=0.011). The reclearance proportion at six months after reinfection was 52% (95%CI: 33-73%). Adjusting for study site, females with IFNL4 (formerly IFNL3 and IL28B) rs12979860 -CC genotype were more likely to reclear (HR:4.16, 95%CI: 1.24-13.94, p=0.021). CONCLUSIONS: Sex and IFNL4 genotype are associated with spontaneous clearance after reinfection.

This work was supported by the National Institutes of Health (NIH; grants U19 AI088791 [to A. L. C.] and U19 AI066345 [to A. Y. K., T. M. A. and B. H. M.]); the National Institute on Drug Abuse, NIH (grants R01 DA031056 [to the InC3 Study], R01 DA033541 [to A. Y. K.], R01 DA016017 [to K. P. and M. M.], and R01 DA15999-01 [to G. J. D., J. G., A. R. L., and M. H.]); the Victorian Operational Infrastructure Support Program (to the Burnet Institute); the National Health and Medical Research Council (postgraduate scholarship to R. S.-D., practitioner research fellowships to G. J. D. and A. R. L., senior research fellowships to M. H. and L. M., career development fellowship to J. G., and project grants 630483 [to the Hepatitis C Virus Incidence and Transmission Study–Community {HITS-c}] and 331312 [to the Networks 2 {N2} project]); Fonds de la Recherche du Québec–Santé (research career awards to J. B. and N. H. S.); an Australian postgraduate PhD award (to B. H.); the Canadian Institutes of Health Research (grants MOP-103138 and MOP-106468 to J. B. and N. H. S.); the Netherlands National Institute for Public Health and the Environment (to the Amsterdam Cohort Study); the University of New South Wales Hepatitis C Vaccine Initiative (to the HITS-c); the Australian Centre for HIV and Hepatitis Virology Research (to the N2 project); and the Centre for Research Excellence into Injecting Drug Use (to M. H., G. J. D., L. M., J. G., and R. S. D.).