Prevalence and Severity of Potential Drug–Drug Interactions in People Living with HIV on Antiretroviral Therapy in the United States

As people living with HIV (PLWH) age, the risk for polypharmacy and potential drug–drug interactions (pDDIs) will likely increase, which may pose clinical challenges and contribute to increased healthcare burden. This retrospective study used administrative claims data (1/1/19–1/31/25) from Optum’s de-identified Clinformatics® Data Mart Database and included adults with ≥ 1 antiretroviral therapy (ART) claim from 1/1/24–12/31/24 (index date: earliest ART claim). The prevalence and severity of pDDIs between ART and each non-ART comedication the PLWH received during the 30-day post-index period were quantified at the ART agent and ART regimen levels. DDI severity was categorized using the University of Liverpool HIV Drug Interactions Resource scale: contraindicated, major, minor, or no interaction. Prevalence of pDDIs was reported as the proportion of PLWH with any pDDI by severity category. Overall, 22,412 PLWH were included; 44.2% had ≥ 1 pDDI classified as contraindicated, major, or minor. At the ART regimen level, contraindicated pDDIs were most prevalent for darunavir/cobicistat/emtricitabine/tenofovir alafenamide (14.4%) and elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate (14.0%). Major pDDIs were observed in up to 66.4% of PLWH receiving certain boosted ART, whereas contraindicated pDDIs were uncommon (< 7%) among PLWH on non-boosted integrase inhibitor- and non-nucleoside reverse transcriptase inhibitor-based regimens. Across commonly prescribed ART regimens, 61.5% to 69.7% of PLWH had either no comedications or only comedications classified as having no interaction, with lower proportions observed for boosted regimens, and major pDDIs were predominantly associated with antidiabetic medications and statins. In this large, real-world claims analysis, pDDIs between ART and non-ART medications were not uncommon in routine clinical practice. As the HIV population continues to age, systematic screening for drug interactions (particularly with comedications for chronic conditions such as diabetes and cardiovascular disease) and thoughtful, individualized ART selection may help mitigate interaction risk and support safe, effective long-term HIV management.