What is the recommended post-exposure prophylaxis (PEP) regimen for occupational exposure to a source with high risk of Human Immunodeficiency Virus (HIV)?

Occupational HIV Post-Exposure Prophylaxis for High-Risk Source

For occupational exposures to a high-risk HIV source, initiate an expanded three-drug antiretroviral regimen immediately—preferably bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) as a single daily tablet, or alternatively dolutegravir plus emtricitabine/tenofovir alafenamide—and continue for 28 days. 1, 2

Immediate Action Protocol

Start PEP as soon as possible, ideally within 1-2 hours of exposure. 1, 2, 3

• Do not delay the first dose while awaiting HIV testing results of either the exposed healthcare worker or confirmation of the source patient's status 1, 3
• PEP remains beneficial even when started beyond 24-36 hours, and should be initiated up to 72 hours post-exposure, though efficacy decreases with time 4
• If questions exist about which specific drugs to use, start the regimen immediately rather than delaying administration 4

Preferred Three-Drug Regimens for High-Risk Exposures

High-risk exposures warrant an expanded three-drug regimen rather than a basic two-drug approach. 4

First-Line Option:

• Bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF): One tablet once daily for 28 days 1, 2

Alternative Option:

• Dolutegravir (DTG) 50mg once daily PLUS emtricitabine/tenofovir alafenamide (FTC/TAF) 200mg/25mg once daily for 28 days 1, 2, 3

Historical Context:

The older 2001 guidelines recommended expanded regimens using combinations like ZDV + 3TC plus a third drug (protease inhibitor or NNRTI) for high-risk exposures 4. However, the 2025 CDC recommendations prioritize integrase inhibitor-based regimens for superior tolerability and efficacy 1, 2.

What Defines "High-Risk" Exposure

High-risk exposures include: 4

• Large-volume blood exposure (e.g., deep injury with large-bore hollow needle, visible blood on device, or needle used in source patient's artery or vein)
• Source patient with high viral load or advanced HIV disease (symptomatic HIV, AIDS, acute seroconversion)
• Percutaneous injuries that are deep rather than superficial
• Exposure to concentrated virus in research or laboratory settings

Duration and Completion

• Complete the full 28-day course if tolerated 4, 2
• PEP may be discontinued only if the source is later confirmed to be HIV-negative 4
• If the source remains unknown or is confirmed HIV-positive, the full 28 days is essential 3

Baseline and Follow-Up Testing

At Initial Presentation (Before Starting PEP):

• Rapid or laboratory-based HIV antigen/antibody combination test 1, 2, 3
• Baseline renal function assessment before initiating tenofovir-based regimens 1, 3
• Assess for medical comorbidities, current medications, and allergies 2

Follow-Up Testing Schedule:

• 4-6 weeks post-exposure: Laboratory-based HIV Ag/Ab test plus diagnostic HIV NAT 2, 3
• 12 weeks post-exposure: Laboratory-based HIV Ag/Ab combination immunoassay and diagnostic HIV NAT 2, 3
• Extended follow-up to 6 months may be considered for standard monitoring 4

Special Populations

Pregnant Healthcare Workers:

• Approach risk assessment and need for PEP as with any other exposed person 4
• Avoid efavirenz (EFV) due to teratogenic effects in primate studies 4
• Avoid stavudine (d4T) plus didanosine (ddI) combination due to reports of fatal lactic acidosis in pregnant women 4
• Discuss potential benefits and risks to both woman and fetus before initiating therapy 3

Renal Impairment:

• Use tenofovir alafenamide (TAF) instead of tenofovir disoproxil fumarate (TDF) for better renal safety profile 3

Source Patient Considerations

• Attempt rapid HIV testing of the source patient if available and consenting 3
• Consider the source patient's antiretroviral treatment history and potential drug resistance when selecting PEP regimen 4
• If source virus is known or suspected to be resistant to specific drugs, select alternative agents; expert consultation is advised but should not delay PEP initiation 4

Monitoring During PEP

• Reevaluate the exposed person within 72 hours post-exposure as additional information becomes available 4
• Monitor for drug toxicity for at least 2 weeks after starting PEP 4, 2
• Provide counseling on precautions to prevent secondary transmission during the follow-up period 4

Critical Pitfalls to Avoid

• Never delay PEP beyond 72 hours—effectiveness drops dramatically with time 1, 2, 3
• Do not wait for source HIV testing results before starting the first PEP dose 1, 3
• Do not use a two-drug regimen for high-risk exposures—current evidence supports three-drug regimens for adequate coverage 4, 3
• Do not stop PEP prematurely if the source remains unknown or is confirmed positive 3
• Assess for drug interactions with the patient's current medications to avoid treatment failure or toxicity 2

Expert Consultation Resources

• The National PEPline (888-448-4911) provides expert consultation for complex cases or questions about drug selection 1, 2
• However, do not delay PEP initiation while awaiting consultation—start therapy immediately and adjust later if needed 1, 2