PrEParing for the unexpected: mechanisms and management of HIV pre-exposure prophylaxis failure

Pre-exposure prophylaxis (PrEP) for HIV is a proven and effective tool for preventing HIV. However, there are instances where individuals taking PrEP have contracted HIV infection. Most of these cases are due to nonadherence to the drug, while other cases of apparent PrEP failure are due to unrecognized HIV infection at baseline. Importantly, there are also now at least three well-documented cases of PrEP failing despite adequate adherence; these are cases of PrEP ‘breakthrough’. This article outlines the potential mechanisms of PrEP failure, as well as how to identify and manage these patients. Finally, we provide a perspective on the future of PrEP as a key tool in preventing HIV worldwide.