In 2009, the regional Drug and Therapeutics Committee (DTC) began a series of meetings with lead specialists in infectious diseases. The role of the DTC was to engage clinicians and ensure commitment to prescribing the least expensive drugs among the clinically equivalent HAARTs (highly active antiretroviral therapy). DTC also led implementation of a national guideline. This study analyses the impact of this process on HAART consumption and expenditure. The HAART consumption and expenditure (2009-2013) was compared to forecasts produced by exponential smoothing (2004-2009). Abrupt switches between drug regimens coincided with the DTC-led meetings. Overall, HAART consumption rose 16%, while price per defined daily dose (DDD) fell 11% and the 2013 expenditure decreased 23%. The consumption of drugs addressed by the guideline rose 48%. Still, the 2013 expenditure was 41.5 million DKK (5.5 million €) (27%) lower than expected, reflecting a fall in price per DDD that coincided with the intervention. The consumption of drugs not addressed by the guideline rose 8.3%, while price per DDD fell 8.5% and the 2013 expenditure was 26.8 million DKK (3.6 million €) (19%) lower than expected. Despite a steadily increasing consumption, significant cost savings followed this DTC-led intervention. This multifaceted approach might be applicable to changing the prescribing of other expensive drug classes.