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This report examines associations between homelessness and HIV risk behaviors among injection drug users (IDUs) in Puerto Rico. The study sample consisted of 557 IDUs who were not in treatment, recruited in inner-city neighborhoods of the North Metro Health Care Region. Subjects were categorized into three groups by residential status (last 30 days): housed, transitionally housed (living with friends, family, or others but considering themselves homeless), and on-the-street homeless (living on the street or in a shelter). Multiple logistic regression models were fitted to assess effects of residential status on each HIV risk behavior after adjusting for sociodemographic and drug-use related covariates. Transitionally housed and on-the-street homeless subjects made up 16% of the total sample. On-the-street homeless IDUs were more likely to test positive for HIV than were transitionally housed and housed IDUs. In the adjusted analysis, on-the-street homeless subjects were significantly more likely to share needles, share rinse water, and practice back loading than the other two groups. Sexual risk behaviors (last 30 days) were not significantly associated with residential status after adjustment. Findings from this study present an added challenge to drug treatment and HIV prevention and treatment programs, to provide services that can address the additional needs of drug users suffering the stressors of homelessness.