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Requiring help injecting has been associated with syringe sharing among injection drug users (IDUs). No prospective study has fully examined this risk factor and its relation to rates of HIV infection. We investigated whether requiring help injecting illicit drugs was a predictor of HIV infection among a prospective cohort of IDUs.The Vancouver Injection Drug User Study is a prospective study of more than 1500 IDUs who have been recruited from the Downtown Eastside of Vancouver since May 1996. At baseline and semiannually, subjects provided blood samples and completed an interviewer-administered questionnaire. The questionnaire elicits demographic data as well as information about drug use, HIV risk behavior, and drug treatment. HIV incidence rates were calculated using Kaplan-Meier methods, and Cox regression determined independent predictors of seroconversion.A total of 1013 baseline HIV-negative participants were eligible for this study. Within this population, 418 (41.3%) participants had required help injecting during the last 6 months at baseline. Participants requiring help injecting were more likely to be female (odds ratio = 2.3, 95% confidence interval [CI]: 1.8-3.0; P < 0.001), were slightly younger (33.5 vs. 34.9 years of age; P = 0.014), and had fewer years of experience injecting drugs (7 vs. 11 years; P ≤ 0.001). Among participants who required help injecting at baseline, cumulative HIV incidence at 36 months was 16.1% compared with 8.8% among participants who did not require help injecting (log-rank, P < 0.001). In an adjusted model controlling for potential confounding variables, being aboriginal (relative hazard [RH] = 1.68, 95% CI: 1.15-2.48), injecting cocaine daily (RH = 2.71, 95% CI: 1.87-3.95), and requiring help injecting (RH = 1.79, 95% CI: 1.23-2.62) remained independent predictors of HIV seroconversion.These data demonstrate the need for interventions to reduce the risk of HIV infection among IDUs who require help injecting.