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.

Medetomidine, a nonopioid sedative not approved for use in humans, has periodically been detected in illegally manufactured opioids across North America since 2022. On May 11, 2024, the Chicago Department of Public Health (CDPH) and the Illinois Department of Public Health were alerted by hospitals and the Illinois Poison Center to an increase in emergency medical services responses for suspected opioid-involved overdoses with atypical symptoms, mostly clustered on Chicago's West Side. CDPH and CDC investigated and identified 12 confirmed, 26 probable, and 140 suspected overdoses involving medetomidine mixed with opioids among patients treated at three hospitals in Chicago's West Side during May 11-17, 2024. Medetomidine had not been previously identified in Chicago's illegal drug supply. Fentanyl was identified in all drug samples and blood specimens containing medetomidine. Most patients were male, non-Hispanic Black or African American, and aged 45-64 years; most patients with confirmed cases experienced bradycardia and had no or only a partial response to naloxone. This cluster is the largest reported for confirmed medetomidine-involved overdoses. Multisector surveillance, including by health care providers, toxicology laboratories, and public health personnel, was essential for quickly identifying and responding to new adulterants in the illegal drug supply. Because all specimens and samples in this investigation that contained medetomidine also contained natural or synthetic opioids, administering naloxone for all suspected opioid-involved overdoses remains crucial.