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Physical activity is beneficial for persons with HIV infection but little is known about the relationships between physical activity, HIV treatment and injection drug use (IDU). This study compared physical activity levels between HIV-negative and HIV-positive injection drug users (IDUs) and between HIV-positive participants not on any treatment and participants on highly active antiretroviral therapy (HAART). Anthropometric measurements were obtained and an interviewer-administered modified Paffenbarger physical activity questionnaire was administered to 324 participants in a sub-study of the AIDS Linked to Intravenous Experiences (ALIVE) cohort, an ongoing study of HIV-negative and HIV-positive IDUs. Generalized linear models were used to obtain univariate means and to adjust for confounding (age, gender, employment and recent IDU). Vigorous activity was lower among HAART participants than HIV-positive participants not on treatment (p=0.0025) and somewhat lower than HIV-negative participants (p=0.11). Injection drug use and viral load were not associated with vigorous activity. Energy expenditure in vigorous activity was also lower among HAART participants than both HIV-negative and HIV-positive participants not on treatment. Thus, HIV-positive participants on HAART spend less time on vigorous activity independent of recent IDU. More research is needed into the reasons and mechanism for the lack of vigorous activities, including behavioral, psychological and physiological reasons. [ABSTRACT FROM AUTHOR]