Antiretroviral therapy (ART) is effective in reducing HIV transmission and mortality, yet daily adherence remains a challenge for many people with HIV (PWH). Suboptimal adherence can lead to virological failure and increased mortality, particularly among those with substance use disorders, such as cocaine use disorder (CUD). The Information-Motivation-Behavioral (IMB) skills model offers a framework to understand and enhance ART adherence by addressing individual and social barriers. In this study, we tested the IMB skills model among 80 cocaine-using PWH currently on ART, and found that behavioral skills significantly predicted adherence. In the extension of the IMB skills model, the addition of practical barriers altered the relationship by showing that motivational barriers such as treatment fatigue and practical barriers significantly affected ART adherence. The findings suggest that for PWH with substance use disorders, addressing practical barriers and motivational factors may be crucial for improving ART adherence, in addition to building behavioral skills.