Currently, the management of comorbidities and polypharmacy in HIV-infected patients requires a coordinated action, with special focus on gender differences. Observational, cross-sectional study was conducted to study the HIV population from Menorca (Illes Balears). Adult HIV-positive individuals on antiretroviral treatment attending the pharmacy service from Hospital Mateu Orfila (Menorca) were included. In a single visit, demographical and clinical characteristics, comorbidities and cotreatments were collected. Anticholinergic burden (Drug Burden Index, DBI), drug-to-drug interactions (BOT PLUS database) and symptoms associated with HIV treatment (HIV-SI index) were assessed. A total of 223 patients were included, 68.2% men, with a median age of 53.00 (44.50-58.00) years, median BMI of 24.07, 47.73% smokers and 9.90% drug consumers. Women had more advanced stages of the disease and significantly more symptoms (cough and anxiety) versus men (p = .033 and p = .048, respectively). Moreover higher exposures to anticholinergic drugs (DBI 0.51 vs. 0.27) were reported, together with more frequency of drug-to-drug interactions (57.7% vs. 37.5%; p = .005) that increased with age. Red interactions were more frequently reported in PI (2.69%), NNRTIs (1.92%) and booster drugs (1.92%). These results support the need to implement specific measures for the management of HIV-infected women and tools to assess polypharmacy and risk of drug-to-drug interactions.