Although these strong outcomes suggest that LETS ACT may be ready for a Stage III dissemination trial, it is of note that there was a significant indirect effect of LETS ACT homework compliance on post treatment substance use and HIV sexual risk behavior via the theoretically proposed BA mechanism of action, environmental reward. In the context of limited access to care, these findings point to the need to identify cost-effective delivery-vehicles to increase treatment engagement outside of clinician sessions. Further, identifying neuroscience based biomarkers (neuromarkers) underlying key theoretical aspects of BA (i.e., reward sensitivity), and their relation to heterogeneity in BA treatment response among substance users with depression, are critical for the identification of accurately targeted interventions.