A Dutch man has contracted HIV while apparently adhering well to the daily regimen of Truvada (tenofovir disoproxil fumarate/emtricitabine) as pre-exposure prophylaxis (PrEP). This is the third case of documented PrEP failure and the first that did not involve a rare drug-resistant strain of HIV. The 50-year-old man, who reported using numerous recreational drugs during sex, was rigorously monitored as part of a PrEP study. This meant that PrEP-adherence diary entries, pill counts and dried blood spot test results were all available, and all indicated he was sticking to the daily regimen. Puzzled by the fact that the man contracted a non-drug-resistant strain of HIV, researchers theorize that his “remarkably high” rate of anal sex partners—he reported 38 to 75 per month—and condomless sex acts may have left him repeatedly exposed to HIV such that he beat the odds of prevention.