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To assess trends in HIV, hepatitis C virus (HCV) and HIV/HCV infection among injecting drug users (IDU) from 1990 to 2001 in New York City. The 1990–2001 time period included a very large expansion of syringe exchange in New York City, from 250 000 to 3 000 000 syringes exchanged annually.Cross-sectional seroprevalence surveys of IDU entering drug abuse treatment in New York City, with sample sizes for HCV of 72 in 1990–1991 and 412 in 2000–2001. A structured risk behavior questionnaire was administered, and HIV and HCV testing were conducted. HCV testing was performed on de-linked stored serum samples.Over the 1990–2001 period, HIV prevalence declined from 54 to 13%. HCV prevalence declined from 80 to 59% among HIV-seronegative individuals, and from 90 to 63% overall. The estimated HCV incidence in 2000–2001 among new injectors was 18 per 100 person-years at risk.The large-scale expansion of syringe exchange was temporally associated with large reductions in both HIV and HCV prevalence. The prevalence and incidence of HCV, however, still remain at high levels among IDU in New York City.