Objectives. We hypothesized that highly disordered neighborhoods would expose residents to environmental pressures, leading to reduced antiretroviral (ARV) medication adherence.

Methods: Using targeted sampling, we enrolled 503 socioeconomically disadvantaged HIV-positive substance users in urban South Florida between 2010 and 2012. Participants completed a 1-time standardized interview that took approximately 1 hour. We tested a multiple mediation model to examine the direct and indirect effects of neighborhood disorder on diversion-related nonadherence to ARVs; risky social networks and housing instability were examined as mediators of the disordered neighborhood environment.

Results: The total indirect effect in the model was statistically significant (P = .001), and the proportion of the total effect mediated was 53%. The model indicated substantial influence of neighborhood disorder on nonadherence to ARVs, operating through recent homelessness and diverter network size.

Conclusions: Long-term improvements in diversion-related ARV adherence will require initiatives to reduce demand for illicit ARV medications, as well as measures to reduce patient vulnerability to diversion, including increased resources for accessible housing, intensive treatment, and support services.