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To identify correlates of enrollment in methadone maintenance treatment programs (MMTP) among a prospective cohort of injection drug users (IDUs) in Baltimore, Maryland.A total of 1480 IDUs undergoing semi-annual HIV tests and interviews were studied between 1994 and 1998, during which time a needle exchange program was introduced. Longitudinal analysis using generalized estimating equations was used to identify correlates of MMTP participation over time.Although similar proportions of HIV-seropositive and -seronegative IDUs enrolled in MMTP during follow-up (26 versus 22%, respectively), correlates of enrollment differed by HIV-serostatus. Among HIV-seropositive participants, older age [adjusted odds ratio (AOR, 1.37)] was associated with enrollment in MMTP. Among HIV-seronegative IDUs, factors associated with not enrolling in MMTP were being African American (AOR, 0.22) and having been recently incarcerated (AOR, 0.62) or homeless (AOR, 0.72). In both groups, females were twice as likely to be enrolled in MMTP, and those with Medicaid were 1.5 times more likely to be enrolled. When behavioral factors were lagged one visit, needle exchange program attendance was positively associated with MMTP enrollment among HIV-negative IDUs (AOR, 2.10); however, this association diminished significantly over time as dedicated treatment slots for needle exchange program participants became saturated.These findings underscore the need to improve access to MMTP, especially to certain subgroups such as African-Americans, the homeless, incarcerated and uninsured. Our data suggest that health care providers and needle exchange programs can facilitate enrollment into MMTP provided that adequate treatment slots are consistently available to this particularly vulnerable population.