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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. The authors suggest that because of common polypharmacy, pharmacists should play an enhanced role in monitoring for drug-drug interactions.