Treatment of HIV infection with highly active antiretroviral therapy (HAART) requires high levels of adherence in order to obtain maximum benefit and minimize the development of antiviral resistance. Many patients in community clinical settings have imperfect adherence that may lead to poor clinical outcomes. The Connecticut HIV Medication Project (CHaMP) is a multidisciplinary program designed to evaluate patients receiving antiviral therapy. Based on results of a multifaceted assessment, a variety of targeted interventions and follow-up are offered. A retrospective analysis was performed on patients who were referred to the program over a 35-month period from March 2002 through January 2005. Two hundred forty-nine patients who were referred for adherence services had baseline and follow-up data available for analysis. Participants who maintained an unchanged antiretroviral regimen experienced a significant increase in self-reported adherence (89.1% to 96.9%, p < 0.001) and likelihood of reporting more than 95% adherence (36.6% to 73.1%, p < 0.001) by 7-day recall. Improvements in plasma HIV viremia (3.10 +/- 1.21 log copies to 2.78 +/- 0.98, p < 0.01) were also demonstrated. Limitations to this study included the unusually high level of baseline adherence, the large fraction of patients (28.6%) who were lost to follow-up, and follow-up that was limited to one time point at 12-16 weeks such that attrition of the intervention effect could not be assessed. The CHaMP experience demonstrates that the development of a multifaceted clinical program can have significant impact on medication adherence and viral burden in HIV infection.