• The CDC now recommends Biktarvy or dolutegravir-based regimens as preferred options for non-occupational HIV PEP, emphasizing their potency and tolerability.
• The updated guidelines stress the importance of initiating PEP as soon as possible, ideally within 24 hours and no later than 72 hours after exposure.
• The guidelines include updated recommendations for HIV testing, including the use of rapid antigen/antibody tests and diagnostic nucleic acid tests (NAT), especially for individuals with recent exposure to long-acting injectable antiretrovirals.

The Centers for Disease Control and Prevention (CDC) has released updated guidelines for non-occupational HIV post-exposure prophylaxis (nPEP), marking the first revision since 2016. The updated guidelines, released on May 6, 2025, recommend newer antiretroviral (ARV) regimens, including Biktarvy and dolutegravir-based combinations, for a 28-day course following potential exposure through sexual contact or injection drug use. These guidelines emphasize the importance of initiating PEP as soon as possible, ideally within 24 hours, and include updated considerations for testing, follow-up, and transitioning individuals to PrEP.

• What: Updated guidelines for non-occupational HIV post-exposure prophylaxis (nPEP) including recommendations for newer antiretroviral regimens and testing protocols.
• Who: The Centers for Disease Control and Prevention (CDC), healthcare providers, and individuals at risk of HIV exposure.
• When: Guidelines updated on May 6, 2025, recommending PEP initiation ideally within 24 hours and no later than 72 hours after exposure.
• Where: United States, with recommendations intended for use by U.S. healthcare professionals.

The updated CDC guidelines represent a significant advancement in HIV prevention strategies, incorporating newer ARV regimens that are more potent, better tolerated, and easier to adhere to. The emphasis on rapid PEP initiation within 24 hours underscores the critical window for preventing HIV acquisition. The guidelines also address the evolving landscape of HIV prevention, including considerations for individuals using PrEP and those with exposure to long-acting injectable ARVs. The inclusion of detailed recommendations for special populations, such as pregnant women and children, further enhances the guidelines' clinical utility. These updates aim to improve PEP access, adherence, and effectiveness, ultimately contributing to the reduction of new HIV infections in the United States.

The CDC's updated guidelines for HIV nPEP provide healthcare professionals with evidence-based recommendations for preventing HIV acquisition following potential exposure. By incorporating newer antiretroviral regimens, emphasizing rapid initiation, and addressing specific clinical scenarios, these guidelines aim to enhance PEP effectiveness and contribute to the ongoing efforts to reduce HIV transmission in the United States. Ongoing research and surveillance are essential to further refine PEP strategies and address emerging challenges in HIV prevention.