Human immunodeficiency virus (HIV) positive individuals who adhere to their antiretroviral (ARV) regimens are more likely to achieve suppressed HIV viral load and improved immunologic response; however, for most patients, medication adherence remains a challenge. Prior studies have shown that clinical pharmacists contribute to the management of HIV-infected patients; but due to variability in clinical responsibilities and study limitations, their value has not been fully realized. The objective of this study was to investigate clinical outcomes of an HIV clinical pharmacist's interventions at Kaiser Permanente Medical Care Program, who utilizes medication expertise to provide recommendations for ARV regimen changes. The pharmacist suggests new ARV regimens in order to attain virologic suppression, improve immunologic response, or minimize ARV adverse effects, while aiming to optimize patients' adherence by decreasing pill burden and/or dosing frequency. This retrospective study assessed the effectiveness of the pharmacist's interventions that occurred between 11 September 2006 and 30 September 2008 on pill burden, dosing frequency, and medication adherence. Additionally, CD4+ cell count and HIV viral load pre- and post-intervention were evaluated. Medication adherence was assessed utilizing electronic pharmacy refill records and calculated based on the formula: [(pills dispensed/pills prescribed per day)/days between refills] x 100. From a cohort of 75 patients, mean daily pill quantity and dosing frequency decreased from 7.2 pills/day and 2.0 times/day in the control phase to 5.4 pills/day and 1.5 times/day in the study phase, respectively ( p < 0.001). Medication adherence increased from a mean of 81% in the control phase to 89% in the study phase ( p = 0.003). Clinical outcomes measured by CD4+cell count and CD4% were statistically improved and more individuals achieved undetectable HIV viral loads postintervention ( p < 0.001). In conclusion, HIV clinical pharmacists may play an important role in reducing pill burden and dosing frequency, increasing medication adherence, and improving clinical outcomes.