Because of the increase in life expectancy in older adults with HIV, the frequency of polypharmacy and drug-drug interaction is increasing. Among 242 50-year-old patients on antiretroviral treatment 148 (61%) were receiving other medications. There were 243 potential drug interactions detected with 197 considered moderate and 46 severe, affecting 110 patients. Generally, the blood levels of the non-HIV medications were higher with this interaction. Statins and inhaled corticosteroids were the most common medications. Interactions with boosted protease inhibitors were more frequent.