OBJECTIVES: The primary purpose of this study was to determine the relationship between psychotropic medication use and adherence to combination antiretroviral therapy.  As a secondary analysis, adherence to combination antiretroviral therapy as measured by proportion of days covered (PDC) was compared to adherence based on the medication possession ratio (MPR) in order to facilitate comparison between the results of this study and those of previous studies evaluating antiretroviral adherence. METHODS: Data were extracted from Texas Medicaid files.  Included subjects were adults with prescription claims for at least three antiretroviral medications indicated for treatment of HIV infection within a 3-month period between 1/1/2004 and 12/31/2004.  PDC was defined as the total number of days during the 12-month follow-up period for which all index antiretroviral medications were available divided by 365 days, while MPR was defined as the average number of days supplied for all antiretroviral medications divided by 365 days (truncated at 100%).  Data were analyzed using descriptive statistics. RESULTS: When measured by PDC, the mean adherence to combination antiretroviral therapy across the entire sample (N = 1,321) was 39.1% ± 34.6%. Mean adherence was markedly greater when measured by MPR at 70.4% ± 33.5%, with a mean difference between the two measures of 31.4% ± 36.8%. CONCLUSIONS: PDC provides a more conservative estimate of adherence to combination antiretroviral therapy than MPR.  MPR results indicate that adherence in this study was similar to that found in previous studies using prescription claims data to evaluate adherence to combination antiretroviral therapy using modified versions of the MPR (72-81%).  Use of PDC to calculate adherence to combination antiretroviral therapy may provide more clinically relevant information than other measures since concomitant use of all medications in the regimen is theoretically required for synergistic viral suppression and optimal HIV outcomes.