Antiretroviral Postexposure Prophylaxis After Sexual, Injection Drug Use, or Other Nonoccupational Exposure to HIV - CDC Recommendations, United States, 2025

Abstract

Nonoccupational postexposure prophylaxis (nPEP) for HIV is recommended when a nonoccupational (e.g., sexual, needle, or other) exposure to nonintact skin or mucous membranes that presents a substantial risk for HIV transmission has occurred, and the source has HIV without sustained viral suppression or their viral suppression information is not known. A rapid HIV test (also referred to as point-of-care) or laboratory-based antigen/antibody combination HIV test is recommended before nPEP initiation. Health care professionals should ensure the first dose of nPEP is provided as soon as possible, and ideally within 24 hours, but no later than 72 hours after exposure. The initial nPEP dose should not be delayed due to pending results of any laboratory-based testing, and the recommended length of nPEP course is 28 days. The recommendations in these guidelines update the 2016 nPEP guidelines (CDC. Updated guidelines for antiretroviral postexposure prophylaxis after sexual, injection drug use, or other nonoccupational exposure to HIV - United States, 2016. Atlanta, GA: US Department of Health and Human Services, CDC; 2017). These 2025 nPEP guidelines update recommendations and considerations for use of HIV nPEP in the United States to include newer antiretroviral (ARV) agents, updated nPEP indication considerations, and emerging nPEP implementation strategies. The guidelines also include considerations for testing and nPEP regimens for persons exposed who have received long-acting injectable ARVs in the past. Lastly, testing recommendations for persons who experienced sexual assault were updated to align with the most recent CDC sexually transmitted infection treatment guidelines. These guidelines are divided into two sections: Recommendations and CDC Guidance. The preferred regimens for most adults and adolescents are now bictegravir/emtricitabine/tenofovir alafenamide or dolutegravir plus (tenofovir alafenamide or tenofovir disoproxil fumarate) plus (emtricitabine or lamivudine). However, the regimen can be tailored to the clinical circumstances. Medical follow-up for persons prescribed nPEP also should be tailored to the clinical situation; recommended follow-up includes a visit at 24 hours (remote or in person) with a medical provider, and clinical follow-up 4-6 weeks and 12 weeks after exposure for laboratory testing. Persons initiating nPEP should be informed that pre-exposure prophylaxis for HIV (PrEP) can reduce their risk for acquiring HIV if they will have repeat or continuing exposure to HIV after the end of the nPEP course. Health care professionals should offer PrEP options to persons with ongoing indications for PrEP and create an nPEP-to-PrEP transition plan for persons who accept PrEP.

FIGURE 1

Study selection process for updating HIV nonoccupational postexposure prophylaxis recommendations — CDC recommendations, United States, 2025 Abbreviations: ARV = antiretroviral; nPEP = nonoccupational postexposure prophylaxis; oPEP = occupational postexposure prophylaxis; PEP = postexposure prophylaxis.

FIGURE 2

HIV nonoccupational postexposure prophylaxis in the setting of possible sexual exposure — CDC recommendations, United States, 2025*^,† Abbreviations: nPEP = nonoccupational postexposure prophylaxis; PrEP = pre-exposure prophylaxis. * Evidence is insufficient to recommend nPEP initiation later than 72 hours postexposure. However, certain experts have argued that risk versus benefit considerations could favor a longer initiation window. ^† See Appendix A for more information on case-by-case determinations. Health care professionals unfamiliar with nPEP should use local infectious diseases or other expert consultation resources or consult the National Clinical Consultation Center PEPline at 888-448-4911 or https://nccc.ucsf.edu/clinician-consultation/pep-post-exposure-prophylaxis, or the Perinatal HIV Line at 888-448-8765 or https://nccc.ucsf.edu/clinician-consultation/perinatal-hiv-aids.

FIGURE 3

HIV nonoccupational postexposure prophylaxis in the setting of possible injection drug use — CDC recommendations, United States, 2025 Abbreviation: nPEP = nonoccupational postexposure prophylaxis. * See Appendix A for more information on case-by-case determinations. Health care professionals unfamiliar with nPEP should use local infectious diseases or other expert consultation resources or consult the National Clinical Consultation Center PEPline at 888-448-4911 or https://nccc.ucsf.edu/clinician-consultation/pep-post-exposure-prophylaxis, or the Perinatal HIV Line at 888-448-8765 or https://nccc.ucsf.edu/clinician-consultation/perinatal-hiv-aids.

FIGURE 4

HIV nonoccupational postexposure prophylaxis in the setting of infective fluid splash or exposure, needle injury, or human bites — CDC recommendations, United States, 2025 Abbreviation: nPEP= nonoccupational postexposure prophylaxis. * See Appendix A for more information on case-by-case determinations. Health care professionals unfamiliar with nPEP should use local infectious diseases or other expert consultation resources or consult the National Clinical Consultation Center PEPline at 888-448-4911 or https://nccc.ucsf.edu/clinician-consultation/pep-post-exposure-prophylaxis, or the Perinatal HIV Line at 888-448-8765 or https://nccc.ucsf.edu/clinician-consultation/perinatal-hiv-aids.