1Burnet Institute, Melbourne 3004, VIC, Australia Department of Epidemiology and Preventive Medicine, Monash University, Melbourne 3004, VIC, Australia.
2The Kirby Institute, UNSW Australia, Sydney NSW 2052, NSW, Australia.
3Department of Medicine, Johns Hopkins University, Baltimore 21205, MD, USA.
4Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco 94143, CA, USA.
5CRCHUM, Université de Montréal, Montreal H2X 3J4, QC, Canada.
6GGD Public Health Service of Amsterdam, Amsterdam 1018 WT, The Netherlands Academic Medical Center, Amsterdam 1105 AZ, The Netherlands.
7Harvard Medical School, Boston 02115, MA, USA.
8Tufts Medical School, Boston 02111, MA, USA Abbvie, Chicago 60064, IL, USA.
9Academic Medical Center, Amsterdam 1105 AZ, The Netherlands.
10School of Medical Sciences, University of New South Wales, Sydney 2052, NSW, Australia.
We aimed to characterize the natural history of hepatitis C virus (HCV) reinfection and spontaneous clearance following reinfection (reclearance), including predictors of HCV reclearance.
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).
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).
Sex and IFNL4 genotype are associated with spontaneous clearance after reinfection.