Polypharmacy and drug-drug interactions in HIV-infected subjects in the region of Madrid, Spain: a population-based study

Drug-drug interactions (DDIs) involving antiretrovirals (ARVs) tend to cause harm if unrecognized, especially in the context of multiple co-morbidity and polypharmacy.; A database linkage was established between the regional drug dispensing registry of Madrid and the Liverpool HIV DDI database (January-June 2017). Polypharmacy was defined as the use of ≥5 non-HIV medications, and DDIs were classified by a traffic-light ranking for severity. HIV-uninfected controls were also included.; A total of 22,945 patients living with HIV (PLWH) and 6,613,506 uninfected individuals had received medications. Antiretroviral therapy regimens were predominantly based on integrase inhibitors (51.96%). Polypharmacy was significantly higher in PLWH (32.94%) than uninfected individuals (22.16%; P<0.001), and this difference was consistently observed across all age strata except for individuals aged ≥75 years. Polypharmacy was more common in women than men in both PLWH and uninfected individuals. The prevalence of contraindicated combinations involving ARVs was 3.18%. Comedications containing corticosteroids, quetiapine, or antithrombotic agents were associated with the highest risk for red-flag DDI, and the use of raltegravir or dolutegravir-based antiretroviral therapy was associated with an adjusted odds ratio of 0.72 (95% confidence interval: 0.60 - 0.88; P=0.001) for red-flag DDI.; Polypharmacy was more frequent among PLWH across all age groups except those aged ≥75 years and was more common in women. The persistent detection of contraindicated medications in patients receiving ARVs suggests a likely disconnect between hospital and community prescriptions. Switching to alternative unboosted integrase regimens should be considered for patients with high risk of harm from DDIs.