OBJECTIVE: To systematically review factors associated with HIV disease progression among illicit drug users, focusing on exposures exogenous to individuals that likely shape access and adherence to HIV treatment. DESIGN: A systematic review of peer-reviewed English-language studies among HIV-seropositive illicit drug users with at least one of these endpoint of interest: a diagnosis of AIDS; death; changes/differences in CD4 cell counts; or changes/differences in plasma HIV-1 RNA levels. METHODS: Articles were included if they reported factors associated with an outcome of interest among a group of illicit drug users. Studies were identified, screened and selected using systematic methods. RESULTS: Of 2668 studies matching the search criteria, 58 (2%) met the inclusion criteria, all but one from North America or western Europe. Overall, 41 (71%) studies contained significant individual-level clinical characteristics or behaviors (e.g. illicit drug use) associated with disease progression. Fifteen studies (26%) identified significant social, physical, economic or policy-level exposures, including incarceration, housing status or lack of legal income. CONCLUSION: Although past studies demonstrate important environmental exposures that appear to shape access to care and subsequent disease progression, the limited literature to examine these factors demonstrates the need for future research to consider risk environment characteristics and the role they may play in shaping health outcomes from HIV infection among drug users through determining access and adherence to evidence-based care.