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There is wide variation in reported risk factors for HIV incidence among injecting drug users by community. Available HIV seroprevalence and incidence data indicate that nearly 60% of HIV infection is associated with injecting drug use in Connecticut and 48% in Massachusetts. Using 12-month follow-up data on 354 initially HIV-negative New England (Massachusetts and Connecticut) methadone treatment clients, we assessed the association between baseline drug use practices, sexual behavior, partner behaviors, and client-reported HIV infection during follow-up. Variables that predicted client-reported positive HIV antibody test results were modeled by Cox proportional hazards regression. HIV infection among those tested was 14.2 per 100 person years (PY) [95% Confidence interval (CI) = 9.5 to 21.3]. For each injection the relative risk (RR) was 1.1 (95% CI = 1.1 to 1.2), for males 3.0 (95% CI = 1.2 to 7.3), for blacks 5.0 (95% CI = 1.6 to 15.5), for Hispanics 3.6 (95% CI = 1.2 to 10.5). Men who used more than one unclean needle per day and had an HIV-infected steady partner had an RR of 28.4 (95% CI = 4.4 to 176.4). For women, using speedball (RR = 6.1, 95% CI = 1.2 to 38.8) and being black (RR = 4.4, 95% CI = 1.0 to 19.8) predicted self-reported HIV infection; having a steady partner who ever injected increased this risk substantially (RR = 65.3, 95% CI = 4.0 to 1046.5). These findings for IDUs in Massachusetts and Connecticut indicate that risk factors for HIV infection for men are consistent with expected transmission by unclean needles with an HIV-infected partner, but a preference for using speedball predicted HIV infection among women IDUs. [ABSTRACT FROM AUTHOR]