Findings to date indicate that it is feasible to deliver a brief behavioral risk reduction/medication adherence group intervention to HIV-infected injection drug users in a community-based setting. HIV infection and substance abuse can result in neurocognitive impairment and this is directly relevant to intervention development, because a significant number of people living with HIV/AIDS have a positive history of substance abuse and being able to successfully participate in behavioral interventions often requires a relatively high level of cognitive performance. The aim of the current study was to evaluate if changes in information, motivation, and behavior skills with respect to medication adherence, sex- and drug-risk behavior outcomes from baseline to post-intervention are predicted by cognitive impairment following the brief four-session Holistic Health for HIV intervention for HIV-infected Drug Users (3H+). Significant associations were found between change in motivation and certain neurocognitive performance domains. Findings suggest that it may be helpful to specifically tailor such behavioral interventions to accommodate cognitive impairment.