Hepatitis C Virus (HCV)–Specific Immune Responses of Long-Term Injection Drug Users Frequently Exposed to HCV

Injection drug users (IDUs) constitute the largest group of HCV-infected people in the United States and account for 42% of new infections [1]. After 10 years of injection drug use, ~90% of IDUs test anti-HCV positive by means of standard EIA [2]; of these IDUs, 80% are persistently infected with HCV [2, 3]. The most common mode of HCV transmission is multiperson use of contaminated syringes and other injection-related paraphernalia [4]. More than 40,000 IDUs live in the San Francisco Bay area [5]. From 1986 through 2005, the Urban Health Study (UHS) recruited active IDUs from street settings in inner-city San Francisco Bay area neighborhoods, counseled them regarding reducing the risk of infection, tested them for HIV antibodies, and referred them to appropriate medical and social services [6-8]. Prospective, semiannual sampling revealed that the prevalence of HCV antibody increased in association with the duration of injection drug use [2, 3, 9, 10], which likely reflects an effect of cumulative exposure. Interestingly, however, the incidence of new HCV infections, as measured by seroconversion, decreased in association with longer durations of injection drug use. This reduction in the incidence of HCV infection did not appear to be a chance phenomenon and was independent of risk behavior (B.R.E., unpublished data), suggesting that seronegative IDUs with a long duration of HCV exposure may have some degree of innate or acquired immunity. In this context, 2 recent epidemiological studies demonstrated that IDUs who successfully cleared HCV in the past have a reduced risk of developing persistent HCV viremia, despite continued injection drug use and continued exposure to HCV [11, 12]. Subjects who had cleared a past HCV infection were 2 times [11] and 4 times [12] less likely to develop persistent HCV infection than were subjects without evidence of past HCV exposure. To identify potential immunological correlates of immune protection, we studied the cellular and humoral immune responses of a subgroup of IDUs in the UHS who reported injection drug use of >10 years’ duration.