HIV-seropositive, active injection-drug users (IDUs), compared with other HIV populations, continue to have low rates of highly active antiretroviral therapy (HAART) use, contributing to disparities in their HIV health outcomes. We sought to identify individual-level, interpersonal, and structural factors associated with HAART use among active IDUs to inform comprehensive, contextually tailored intervention to improve the HAART use of IDUs. Prospective data from three semiannual assessments were combined, and logistic general estimating equations were used to identify variables associated with taking HAART 6 months later. Participants were a community sample of HIV-seropositive, active IDUs enrolled in the INSPIRE study, a U.S. multisite (Baltimore, Miami, New York, San Francisco) prevention intervention. The analytic sample included 1,225 observations, and comprised 62% males, 75% active drug users, 75% non-Hispanic blacks, and 55% with a CD4 count <350; 48% reported HAART use. Adjusted analyses indicated that the later HAART use of IDUs was independently predicted by patient-provider engagement, stable housing, medical coverage, and more HIV primary care visits. Significant individual factors included not currently using drugs and a positive attitude about HAART benefits even if using illicit drugs. Those who reported patient-centered interactions with their HIV primary care provider had a 45% greater odds of later HAART use, and those with stable housing had twofold greater odds. These findings suggest that interventions to improve the HIV treatment of IDUs and to reduce their HIV health disparities should be comprehensive, promoting better patient-provider engagement, stable housing, HAART education with regard to illicit drug use, and integration of drug-abuse treatment with HIV primary care.