A 44-year-old Canadian man has become the first person to experience a documented case of presumed failure on Truvada (tenofovir/emtricitabine) as pre-exposure prophylaxis (PrEP) while apparently adhering well to the daily drug regimen. He contracted a multidrug-resistant strain of HIV. A research team analyzed multiple layers of evidence to support the man’s insistence that he had been taking Truvada regularly, including pharmacy records and two different kinds of blood tests to measure drug levels. The team concluded that it is indeed possible for individuals who are adherent to PrEP to contract HIV if they are exposed to a virus that is resistant to both drugs included in Truvada, as occurred with this man. While his case is concerning, experts in the PrEP field believe that such failures of PrEP will likely remain rare.