Emtricitabine/tenofovir disoproxil fumarate (FTC/TDF; Truvada®) given as pre-exposure prophylaxis (PrEP) successfully blocks HIV when taken once daily prior to potential HIV exposure. A 22-year-old male reported difficulty swallowing FTC/TDF for PrEP and subsequently began chewing the FTC/TDF tablets. Monthly urine samples assessed using liquid chromatography-tandem mass spectrometry (LC-MS/MS) indicated tenofovir levels >1,000 ng/ml, indicative of protection from HIV acquisition, over a 48-week period. Data from observational studies of HIV-positive patients details the successful treatment of HIV using crushed FTC/TDF delivered via feeding and gastronomy tubes while small, randomized trials of healthy volunteers demonstrate bioequivalence between whole and crushed FTC/TDF.