What Are the Latest Recommendations for Occupational HIV Post-Exposure Prophylaxis in Healthcare Settings?

Brief History of HIV Post-Exposure Prophylaxis
By the end of 2024, an estimated 40.8 million people worldwide were living with human immunodeficiency virus (HIV).1 Approximately 0.7% of adults aged 15 to 49 are affected globally, though the impact of HIV varies greatly across different countries and regions. Because of factors such as high‑risk behaviors, heterosexual transmission, societal changes, and increasing interaction among diverse populations, the possibility of HIV exposure remains a genuine concern in daily life.2 This risk is especially relevant for health care workers, including surgeons and anesthetists.

From 1985 to 2013, the Centers for Disease Control and Prevention (CDC) received reports of 58 confirmed and 150 possible cases of occupational HIV transmission in the United States.3 Only one confirmed case occurred after 1999, involving a laboratory employee who was accidentally stuck with a needle containing live HIV. Of the 58 confirmed occupational infections, most were due to percutaneous injuries, 5 resulted from mucocutaneous exposure, 2 involved both types of exposure, and 2 had unknown exposure routes. No documented cases of occupationally acquired HIV have been reported in the United States since 2008.4

Guidance on post‑exposure prophylaxis (PEP) for HIV has expanded steadily since the first United States recommendations in 1996, which endorsed zidovudine and lamivudine for occupational exposure.5 Evidence from animal models showing that mucosal transmission could be prevented after exposure helped guide the creation of non‑occupational PEP guidelines in 2005. As newer antiretrovirals became available, recommendations evolved accordingly; HIV care has advanced dramatically with safer and more effective antiretrovirals, single pill regimens, and better diagnostic tools. However, optimizing PEP remains challenging.

Modern guidelines now favor tenofovir‑based regimens and integrase inhibitors because of improved tolerability.5 Certain older drug classes are discouraged, including first‑generation non-nucleotide reverse transcriptase inhibitors (NNRTIs) such as nevirapine, linked to hepatotoxicity, and efavirenz, associated with insomnia and mood changes that contribute to discontinuation.

Rationale for Occupational HIV Post-Exposure Prophylaxis
After a needlestick or mucous membrane exposure to blood from a person with HIV, the virus first replicates in dendritic cells at the site of entry before moving through the lymphatic system and becoming a systemic infection.6 This early delay provides a brief window in which HIV PEP can stop the virus from establishing a long-term infection.

A landmark 1997 case control study showed that taking zidovudine for at least 4 weeks lowered the risk of HIV infection by 81% when started within 4 hours after a needlestick injury in health care workers.6,7 These findings, combined with CDC guidance, led to widespread adoption of occupational PEP in the late 1990s.

Since 2000, occupational HIV transmission in the United States has become extremely rare, indirectly supporting the effectiveness of PEP; additional evidence comes from small observational studies in both humans and animal models.6 Although randomized controlled trials of occupational PEP have not been done, and are unlikely because of ethical and practical barriers, the available data strongly support offering PEP to health care workers after potential HIV exposure.

National Guidance
In 2022, the CDC convened a working group composed of representatives from Department of Health and Human Services (HHS) agencies to identify priority areas for revision and conduct systematic reviews that informed updated recommendations to the 2013 US Public Health Service (PHS) Guidelines for the Management of Occupational Exposures to Human Immunodeficiency Virus and Recommendations for Postexposure Prophylaxis.4 The updated guidance was published in 2025.

Key updates since the 2013 PHS guidelines include:

  • Revised antiretroviral regimens for post‑exposure prophylaxis (PEP)
  • A shorter timeline for follow‑up HIV testing after exposure
  • Removal of routine laboratory monitoring for antiretroviral toxicity
  • Guidance related to exposures involving source patients with undetectable viral loads

Selecting an appropriate PEP regimen can be challenging, as clinicians must first assess whether the exposure truly poses a risk that justifies PEP, and many providers have limited experience prescribing these medications.4 To support consistent and effective management, the guideline outlines the necessary infrastructure and standard practices. A 3‑drug regimen has long been the standard for PEP, and newer integrase‑based antiretroviral options are generally better tolerated than older, pre‑ integrase strand transfer inhibitor (INSTI) agents. The preferred regimens listed in Table 1 are associated with mild or manageable adverse effects and have relatively few drug-drug interactions. No occupational HIV transmissions have been documented among healthcare personnel who used the raltegravir + tenofovir DF + emtricitabine regimen, which was the preferred PEP option in the 2013 USPHS guidelines. Its removal from the list of preferred and alternative regimens in Table 1 is not due to concerns about efficacy, but rather because it requires multiple daily doses and newer, once‑daily antiretroviral combinations are now available.

Table 1. The initial preferred and alternative HIV PEP regimen for healthcare personnel4
Preferred RegimenAlternative Regimen

Healthcare personnel without conditions specified*		Integrase Strand Transfer Inhibitors PLUS 2 Nucleoside Reverse Transcriptase Inhibitors:
  1. Bictegravir/emtricitabine/tenofovir alafenamide
  2. Dolutegravir PLUS (tenofovir alafenamide OR tenofovir disoproxil fumarate) PLUS (emtricitabine OR lamivudine)
Boosted Protease Inhibitor PLUS 2 Nucleoside Reverse Transcriptase Inhibitors:
  1. Darunavir and cobicistat OR darunavir and ritonavir PLUS (tenofovir alafenamide OR tenofovir disoproxil fumarate) PLUS (emtricitabine OR lamivudine)
Abbreviations: HIV= human immunodeficiency virus ; PEP= post‑exposure prophylaxis;
*Other conditions that have separate medication guidance include: pregnancy, moderate renal dysfunction (creatinine clearance 30–49 mL/min); severe renal dysfunction (creatinine clearance <30 mL/min) and on hemodialysis; severe renal dysfunction (creatinine clearance <30 mL/min) not on hemodialysis; hepatic impairment (Child-Pugh A or B); hepatic impairment (Child-Pugh C)

Conclusion
Occupational HIV transmission in the United States has become extremely uncommon, yet PEP remains a critical intervention for protecting healthcare personnel after potential exposure. Early virologic research demonstrated that HIV replication begins locally before becoming systemic, which creates a short window in which antiretroviral therapy can prevent infection. This evidence, along with early case control data, established the foundation for widespread PEP use. Modern antiretroviral therapy has advanced significantly, offering safer and more tolerable options than earlier regimens. The 2025 USPHS guideline update reflects these improvements by recommending simplified integrase inhibitor-based regimens, shortening follow up testing intervals, and providing clearer guidance for exposures involving virally suppressed source patients. As a result, clinicians now have more streamlined, evidence-based recommendations that support rapid decision making and effective management of occupational HIV exposures, helping maintain a strong layer of protection for the healthcare workforce.

References

  1. World Health Organization. HIV. Published July 15, 2025.Accessed January 21, 2026. https://www.who.int/data/gho/data/themes/hiv-aids
  2. Wyżgowski P, Rosiek A, Grzela T, Leksowski K. Occupational HIV risk for health care workers: risk factor and the risk of infection in the course of professional activities. Ther Clin Risk Manag. 2016;12:989-994. Published 2016 Jun 14. doi:10.2147/TCRM.S104942
  3. Joyce MP, Kuhar D, Brooks JT. Notes from the field: occupationally acquired HIV infection among health care workers – United States, 1985-2013. MMWR Morb Mortal Wkly Rep. 2015;63(53):1245-1246.
  4. Kofman AD, Struble KA, Heneine W, et al. 2025 US Public Health Service Guidelines for the Management of Occupational Exposures to Human Immunodeficiency Virus and Recommendations for Post-exposure Prophylaxis in Healthcare Settings. Infect Control Hosp Epidemiol. 2025:46:863-73. https://doi.org/10.1017/ice.2025.10254
  5. Mayer KH, Allan-Blitz LT. Post-exposure prophylaxis to prevent HIV: new drugs, new approaches, and more questions. Lancet HIV. 2023;10(12):e816-e824. doi:10.1016/S2352-3018(23)00238-2
  6. Core concepts – Occupational postexposure prophylaxis – Prevention of HIV – National HIV curriculum. Updated December 1, 2025. Accessed January 21, 2026. https://www.hiv.uw.edu/go/prevention/occupational-postexposure-prophylaxis/core-concept/all
  7. Cardo DM, Culver DH, Ciesielski CA, et al. A case-control study of HIV seroconversion in health care workers after percutaneous exposure. Centers for Disease Control and Prevention Needlestick Surveillance Group. N Engl J Med. 1997;337:1485-90.

Prepared by:
Faria Munir, PharmD, MS, BCPS
Clinical Assistant Professor, Drug Information Specialist
University of Illinois at Chicago Retzky College of Pharmacy

February 2026

The information presented is current as January 21, 2026. This information is intended as an educational piece and should not be used as the sole source for clinical decision-making.