What is the recommended post-exposure prophylaxis (PEP) regimen for a needlestick injury when the source patient's Human Immunodeficiency Virus (HIV) status is unknown?

PEP Recommendation for Needlestick Injury with Unknown Source HIV Status

When the source patient's HIV status is unknown after a needlestick injury, initiate a case-by-case determination that generally favors starting PEP immediately while attempting to determine the source's HIV status, then discontinue if the source is confirmed HIV-negative. 1

Immediate Action Protocol

Start PEP as soon as possible—ideally within 1-2 hours, but no later than 72 hours after the needlestick injury. 2, 3 The efficacy of PEP decreases significantly after 24-36 hours, though benefit may still exist even when started beyond this window. 1

• Do not delay the first dose while awaiting HIV testing results of either the exposed healthcare worker or the source patient. 2, 3
• Treat this as an urgent medical concern requiring immediate intervention. 1

Risk Assessment for Unknown Source Status

The decision to initiate PEP when source HIV status is unknown requires evaluating: 1

• Type of exposure: Hollow-bore needles that have been placed in a vein or artery carry higher risk than solid needles. 4
• Depth of injury: Deeper penetration increases transmission risk. 4
• Visible blood on the device: Presence of blood significantly elevates risk. 4
• Epidemiologic likelihood: Consider whether the source patient belongs to a high HIV prevalence population (injection drug users, men who have sex with men, commercial sex workers, individuals from high-prevalence geographic areas). 4, 3

Recommended PEP Regimen

Initiate a standard three-drug regimen immediately for unknown source status exposures: 2, 3

Preferred Single-Tablet Option:

• Bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF): One tablet once daily for 28 days. 2, 3

Alternative Multi-Tablet Option:

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

Note: While older 1998 guidelines suggested two-drug regimens (ZDV and 3TC) for unknown source status, 1 current 2025 recommendations favor three-drug regimens for all nonoccupational and most occupational exposures to ensure adequate coverage. 2, 3

Source Patient Testing Strategy

Attempt rapid HIV testing of the source patient immediately if they are available and consent to testing. 1, 3

• Use rapid HIV test kits or laboratory-based antigen/antibody combination tests to facilitate point-of-care decision making. 5, 6
• Implementing "stat" workflow protocols for source patient testing can reduce order-to-result intervals from 195 minutes to 156 minutes and dramatically decrease unnecessary PEP dispensing from 50% to 23%. 6
• If the source is confirmed HIV-negative, PEP can be discontinued. 1, 2
• If the source tests positive or remains unknown, complete the full 28-day course. 2, 3

Baseline and Follow-Up Testing for Exposed Healthcare Worker

Before starting PEP (but without delaying the first dose): 2, 3

• Perform rapid or laboratory-based HIV antigen/antibody combination test. 2, 3
• Assess baseline renal function before initiating tenofovir-based regimens. 2

Follow-up testing schedule: 2, 3, 5

• 4-6 weeks post-exposure
• 12 weeks post-exposure (final test if using fourth-generation combination tests)
• Some protocols recommend 6-month testing, though this may not be necessary with modern testing methods. 1, 5

Duration and Completion

Complete the full 28-day course of PEP if the source remains unknown or is confirmed HIV-positive. 2, 3 Do not stop prematurely, as the full duration is essential for efficacy. 1

Special Considerations

For pregnant healthcare workers: 1

• Approach risk assessment and PEP need identically to non-pregnant workers.
• Discuss potential benefits and risks to both the woman and fetus before initiating therapy.

For renal impairment: 2

• Use tenofovir alafenamide (TAF) instead of tenofovir disoproxil fumarate (TDF) as TAF has better renal safety profile.

Expert Consultation Resources

For complex cases or questions about drug selection, contact the National Clinical Consultation Center PEPline at 888-448-4911. 2, 4 However, do not delay PEP initiation while awaiting consultation—start therapy immediately and adjust based on expert guidance if needed. 2

Critical Pitfalls to Avoid

• Never delay PEP beyond 72 hours, as effectiveness drops dramatically with time. 2, 4, 3
• Do not wait for source HIV testing results before starting the first PEP dose—initiate immediately and adjust later if source is confirmed negative. 2, 3
• Do not use a two-drug regimen for unknown source status—current guidelines favor three-drug regimens for adequate coverage. 2, 3
• Do not stop PEP prematurely if the source remains unknown—complete the full 28 days. 2, 3
• Do not attempt to test the needle itself for HIV, as this is unreliable and not recommended. 4

Managing Side Effects to Ensure Adherence

Common side effects include nausea and gastrointestinal symptoms. 4 Prescribe antiemetics or anti-diarrheal agents proactively to improve adherence and ensure completion of the 28-day course. 4