Update on HIV Preexposure Prophylaxis: Effectiveness, Drug Resistance, and Risk Compensation

In 2019, the US government launched an initiative to decrease new HIV infections by 90% over the next decade. Studies have demonstrated the efficacy of HIV preexposure prophylaxis (PrEP) for high-risk populations, and the United States Preventative Services Task Force has issued a grade A recommendation for PrEP, indicating substantial net benefit. However, questions have been raised about the effectiveness of PrEP in clinical settings and whether PrEP use might promote antiretroviral drug resistance and increased sexual risk behaviors, which could increase transmission of bacterial sexually transmitted infections. In this narrative review, we summarize recent evidence of the effectiveness of PrEP when provided in clinical and community settings, the emergence of antiretroviral drug resistance during PrEP use, and associations between PrEP use and increased sexual risk behaviors. We also review novel PrEP modalities that are being developed to optimize PrEP acceptability, adherence, and effectiveness.

Studies suggest that PrEP is effective when provided in clinical settings. However, PrEP uptake and impact have been limited in the USA thus far, and major disparities in access to PrEP exist. In addition, there is evidence that drug resistance can occur with PrEP use, particularly with inadvertent PrEP use during undiagnosed acute HIV infection. Risk compensation can also occur with PrEP use and has been associated with increased sexually transmitted infections. Promising new modalities for PrEP could expand options. PrEP has strong potential to decrease HIV incidence. However, disparities in access must be addressed to ensure equity and impact for PrEP. While drug resistance and risk compensation can occur with PrEP use, these are not valid reasons to withhold PrEP from patients given its substantial protective benefits.