Background: Neither previous hepatitis C virus (HCV) infection nor vaccination with HCV-derived antigens protects against reinfection. However, HCV infection and vaccination in chimpanzees has been shown to reduce the magnitude and duration of viraemia with re-challenge. We aimed to establish whether similar immunity could be achieved in man. Methods: From a study of injecting drug users, we identified 164 people who had no evidence of previous HCV infection and 98 individuals who had been previously, but were not currently, infected with HCV. We compared the incidence and persistence of HCV viraemia in these two groups over four consecutive 6-month periods. Findings: Of participants without previous infection, the incidence of HCV infection was 21% (35/164). By contrast, people previously infected were half as likely to develop new viraemia (12% [12/98]), even after accounting for risk behaviour (hazard ratio, 0·45; 95% CI 0·23-0·88). Furthermore, in HIV-1-negative people, those previously infected were 12 times less likely than people infected for the first time to develop persistent infection (odds ratio 0·05, 95% CI 0·01-0·30), and median peak HCV RNA concentration was two logs lower. HCV persisted in six of six HIV-1-positive people, even in one man who had previously cleared HCV infection when he was HIV-1 negative. Interpretation: There is an alarming frequency of HCV infection and persistence among injecting drug users. Our data suggest that immunity against viral persistence can be acquired, and that vaccines should be tested to reduce the burden of HCV-related liver disease.
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