BACKGROUND:Individuals with HIV disease often must adhere to complex medication regimens. To date, regimen complexity has not been examined in the literature using standardized procedures incorporating all important elements of antiretroviral (ARV) regimens. OBJECTIVE:This article presents a novel method of quantifying regimen complexity using objective criteria addressing the factors that may complicate adherence to ARV regimens. METHODS:Part 1 of this article describes the development of the Antiretroviral Regimen Complexity (ARC) Index scoring system. Based on input from pediatric and adult patients, caregivers of pediatric patients, and health care professionals, this comprehensive system includes the number of medications, dosing schedules, administration methods, special instructions, and required preparations associated with ARV regimens. Weights are applied for each of these factors to produce an overall score representing the regimen's level of complexity. Part 2 of this article presents reliability and validity data for the system. RESULTS:The ARC Index demonstrates excellent test-retest and interrater reliability as well as strong construct and discriminant validity. An on-line version of this system minimizes computation errors. CONCLUSIONS:Although modifications may be necessary for patients requiring nonstandard dosing instructions, preliminary evidence supports the utility of this measure as a reliable and valid indicator of the complexity of antiretroviral treatment regimens.