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Studies of HIV-positive patients have consistently shown that drug users, in particular injection drug users (IDU), are far more likely to have hepatitis C virus (HCV) infection than other patient groups. HIV incidence and prevalence in IDU has declined in recent years, but HCV remains endemic in this population. HCV antibody prevalence among non-injection users of drugs such as heroin and cocaine is between 5 and 30%, although there are scant data on specific transmission risk behavior. The control of HIV/HCV co-infection must address HCV prevention. Epidemiological studies have suggested that HCV prevalence in IDU is subject to various influences, some of which may be modifiable by interventions. However, studies have not shown consistent effects of various prevention strategies on HCV transmission, including studies of HCV screening and education, drug treatment or needle exchange. Although some large cross-sectional studies in regions where needle exchange is available to a large number of drug injectors have reported declining HCV prevalence, the scale of services needed is a matter of considerable debate and has not been systematically quantified. Priorities for research related to the prevention of HIV/HCV co-infection should include estimating the effect on disease occurrence of eliminating specific risk factors, and specifying the level of resources needed to alter HCV incidence.