Frequent multiple hepatitis C virus infections among injection drug users in a prison setting

Recent data indicate that multiple hepatitis C virus (HCV) infections (mixed infection, superinfection, and reinfection) are common among injection drug users (IDUs). In this study, we identified and characterized multiple HCV infection episodes among HCV-seronegative IDU prison inmates (n = 488) enrolled in the Hepatitis C Incidence and Transmission Study cohort. Incident HCV infection with detectable HCV RNA was identified in 87 subjects, 48 of whom completed additional follow-up to screen for reinfection or superinfection. All HCV RNA-detectable samples were tested for multiple infection through a series of specifically designed nested reverse-transcription polymerase chain reaction (nRT-PCR) with sequencing and HCV RNA level measurement. Sequencing revealed that 22 of 87 (25.3%) subjects were infected by two or more viruses. Nine (10.3%) subjects were designated as prevalent cases of incident mixed infection, because two distinct HCV strains were detected at the first viremic time point. Fifteen further cases of multiple HCV infection (superinfection or reinfection) were identified, two of which also showed baseline incident mixed infections. The incidence of new HCV infection (superinfection and reinfection) during follow-up was 40/100 person-years (95% confidence interval, 33-44/100 person-years). Spontaneous clearance of viruses from one subtype and persistence of the other subtype after mixed infection was observed in eight subjects. In these subjects, the virus with higher HCV RNA levels superseded the other.

This study comprehensively analyzed frequent multiple HCV infections in a high-risk cohort and provides further insight into infection dynamics and immunity after exposure to variant viral strains. The data presented suggest that HCV RNA levels play an important role in viral competition.