HIV-positive people who use drugs (PWUDs) are particularly vulnerable for suboptimal access to highly active antiretroviral therapy (HAART). We conducted a systematic review to identify factors associated with suboptimal HAART access among this population. Studies evaluating HAART access among active PWUDs as a primary outcome, presenting multivariate analysis and conducted after January 1997 were included. Of 122 studies matching the search criteria, only 14 (11.4%) met the inclusion criteria. All selected studies were prospective cohorts and included young adults, 13 were conducted in North America or western Europe and one in Ukraine. Selected studies measured HAART access using different strategies, however, all identified PWUDs as less likely to receive HAART, when compared to those who never used drugs or former PWUDs. Additional factors associated with suboptimal HAART access include: recent incarceration, lack of health insurance, unstable housing, depression, non white ethnicity, female PWUDs, and health professionals stigma/ prejudice. Factors associated with higher rates of HIV-treatment access included: alcohol and/ or drug addiction treatment (especially methadone maintenance therapy), regular source of primary care, treatment and care from the same provider (most of the time) and larger physician experience in HIV-management. PWUDs face a synergy of social and structural factors that influence their suboptimal access to HAART, struggling with poor living conditions, inadequate access to specialized care and stigma/discrimination from health professionals. Renewed strategies and effective interventions should be developed and scaled-up, in order to assure equitable HAART access, decrease morbidity and mortality among PWUDs.