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Antiretroviral therapy administration is challenging in patients with HIV requiring enteral nutrition. There are limited pharmacokinetic data available regarding the absorption of crushed rilpivirine (RPV) and its impact on drug bioavailability, plasma concentrations and, consequently, the efficacy of treatment. We present the case of a 60-year-old woman with HIV diagnosed with squamous cell carcinoma who needed enteral administration of antiretroviral therapy following the insertion of a gastrotomy tube in September 2018. Initially, the patient was treated with a daily dose of RPV 25 mg, dolutegravir 50 mg and emtricitabine 200 mg. The treatment was later intensified with darunavir boosted with ritonavir. RPV and dolutegravir were crushed, dissolved in water and administered via a percutaneous endoscopic gastrostomy tube. Therapeutic drug and viral load monitoring determined the adequacy of enteral antiretroviral dosing. RPV plasma concentrations remained within the expected therapeutic range of 43-117 ng/mL, with only 1 below the currently used 50 ng/mL efficacy threshold. After the treatment intensification with darunavir boosted with ritonavir, the patient achieved an undetectable viral load. While we observed satisfactory RPV plasma concentrations, it is essential to maintain strict monitoring of administration method, plasma concentrations and virological responses when initiating treatment with crushed RPV. Hence, additional pharmacokinetic data are necessary to ensure the effective enteral administration of RPV and to establish the best antiretroviral dosing regimens., (© 2024 British Pharmacological Society.)