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Despite the beneficial effect of the HAART, adverse reactions and drug interaction have been observed. Abnormalities in lipid and glucose metabolism make HIV-positive patients to high risk for the development of coronary heart disease and diabetes, respectively. Besides adverse reactions, drug interaction with other medication can also be observed. In fact, drug interaction may interfere in the periodontal therapy in HIV-infected individuals. For instance, fluconazole, ketoconazole, itraconazole, metronidazole, ciprofloxacin, midazolam and triazolam can interact with some antiretroviral medications, such as zidovudine, nevirapine and ritonavir. The aim of the current study was to show to periodontists and general dental practitioners the importance of understanding the drug interaction in HIV-infection in order to establish a better control during periodontal treatment.