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Objective: Drug use and receipt of highly active antiretroviral therapy (HAART) were assessed in HIV-infected persons from the Comprehensive Care Center (CCC; Nashville, TN) and Johns Hopkins University HIV Clinic (JHU; Baltimore, MD) between 1999 and 2005., Methods: Participants with and without injection drug use (IDU) history in the CCC and JHU cohorts were evaluated. Additional analysis of persons with history of IDU, non-injection drug use (NIDU), and no drug use from CCC were performed. Activity of IDU and NIDU also was assessed for the CCC cohort. HAART use and time on HAART were analyzed according to drug use category and site of care., Results: 1745 persons were included from CCC: 268 (15%) with IDU history and 796 (46%) with NIDU history. 1977 persons were included from JHU: 731 (35%) with IDU history. Overall, the cohorts differed in IDU risk factor rates, age, race, sex, and time in follow-up. In multivariate analyses, IDU was associated with decreased HAART receipt overall (OR = 0.61, 95% CI: [0.45-0.84] and OR = 0.58, 95% CI: [0.46-0.73], respectively for CCC and JHU) and less time on HAART at JHU (0.70, [0.55-0.88]), but not statistically associated with time on HAART at CCC (0.78, [0.56-1.09]). NIDU was independently associated with decreased HAART receipt (0.62, [0.47-0.81]) and less time on HAART (0.66, [0.52-0.85]) at CCC. These associations were not altered significantly whether patients at CCC were categorized according to historical drug use or drug use during the study period., Conclusions: Persons with IDU history from both clinic populations were less likely to receive HAART and tended to have less cumulative time on HAART. Effects of NIDU were similar to IDU at CCC. NIDU without IDU is an important contributor to HAART utilization.