The emergence of hepatitis D virus (HDV) infection in the era of widespread HBV vaccination has not been described before. We aimed to investigate the changing epidemiology of HDV infection among high- and low-risk populations after an outbreak of human immunodeficiency virus (HIV) infection among injection drug users (IDUs) in Taiwan. A prospective, multicenter, cohort study of 2,562 hepatitis B surface antigen (HBsAg)-positive individuals was conducted to determine the prevalence, genotype, and risk factors of HDV infection from 2001 through 2012. The prevalence rates of HDV infection were 74.9%, 43.9%, 11.4%, 11.1%, and 4.4% among HIV-infected IDUs, HIV-uninfected IDUs, HIV-infected men who have sex with men, HIV-infected heterosexuals, and the general population of HBsAg-positive subjects, respectively. A significant increase in the trend of HDV prevalence from 38.5% to 89.8% was observed in HIV-infected IDUs (odds ratio=3.06; 95% confidence interval: 1.68-5.56; P=0.0002). In multivariate analysis, injection drug use, hepatitis C virus infection, HIV infection, serum HBsAg level ≧250 IU/mL, duration of drug use, and older age were significant factors associated with HDV infection. HDV genotype IV (72.2%) was the prevalent genotype circulating among IDUs, whereas genotype II was predominant in the non-IDU populations (73.3%). In the HIV cohort born after 1987 who were HBsAg negative, over half (52.9%) had antibody to hepatitis B surface antigen antibody levels of <10 mIU/mL and there was a significantly higher HBsAg seroprevalence in the HIV cohort, compared to the control group (8.1% vs. 0.0%; P=0.02). Conclusion: In the era of HBV vaccination, IDUs and HIV-infected individuals have emerged as high-risk groups and a reservoir for HDV infection. Effective strategies are needed to curb the reemerging epidemic of HDV infection in these high-risk groups.
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