OBJECTIVES: Fixed-dose combination (FDC) products consisting of ≥2 antiretrovirals in one tablet improve adherence compared to the same agents taken separately. The impact of FDC products on adherence to other regimen components has not been assessed. We used pharmacy records to evaluate whether an FDC product improves HIV patients’ adherence to a 3rd regimen agent. METHODS: Data from 1997 - 2005 were taken from IHCIS Managed Care Benchmark Database, a national sample of 30 health plans covering ~38M lives. We compared adherence to the 3rd regimen component among patients with ≥ 1 pharmacy claim for the FDC Epzicom (abacavir sulfate 600 mg + lamivudine 300 mg) versus 2 NRTIs as separate pills (SP). Adherence was measured as the medication possession ratio (MPR). Multivariate logistic regression compared treatment groups based on the likelihood of achieving ≥ 95% adherence, with sensitivity analyses across other adherence thresholds. Multivariate linear regression assessed the effect of treatment group on MPR as a continuous variable. Covariates included age, gender, insurance payer type, year of study drug initiation, presence of mental health and substance abuse disorders, and 3rd agent class. RESULTS: The sample consisted of 650 FDC and 1947 SP patients. Unadjusted mean adherence to the 3rd agent was higher in the FDC than the SP group (0.92 vs 0.85; p<0.0001). Adjusting for covariates, FDC patients were 48% and 39% more likely to achieve 95% and 90% adherence to the 3rd agent, respectively (p<0.05 for each). These results did not hold for other MPR specifications. CONCLUSIONS: For patients enrolled in managed care plans, use of an FDC appears to substantially improve adherence to a 3rd agent and the likelihood of achieving the accepted standard for adherence to HIV therapy of 95%. FDCs may improve overall adherence by increasing adherence to both the backbone and the 3rd component of the regimen.