What is the recommended post-exposure prophylaxis (PEP) regimen for a human immunodeficiency virus (HIV) infected needle prick exposure?

Post-Exposure Prophylaxis for HIV-Infected Needle Stick Injury

Initiate bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) as a single tablet once daily for 28 days immediately after an HIV-infected needle stick, starting within 1-2 hours if possible, but no later than 72 hours post-exposure. 1, 2, 3

Immediate Action Protocol

Start PEP immediately—do not delay for any reason. The first dose should be administered as soon as possible, ideally within 24 hours, as efficacy decreases significantly with each passing hour. 1, 2, 3 Even if the source patient has an undetectable viral load, PEP is still indicated for occupational exposures from known HIV-positive sources. 1

Critical Timing Window

• Optimal window: Within 1-2 hours of exposure 1
• Acceptable window: Within 24 hours 2, 3
• Maximum window: 72 hours (efficacy drops substantially after this) 1, 2, 3
• Do not delay the first dose while awaiting HIV testing results, source patient viral load confirmation, or laboratory results 1, 2, 3

Preferred Medication Regimens

First-Line Regimen (Single Tablet)

Bictegravir 50mg/emtricitabine 200mg/tenofovir alafenamide 25mg (BIC/FTC/TAF) - one tablet once daily for 28 days 1, 2, 3

This single-tablet regimen maximizes adherence and is the CDC's preferred choice. 3

Alternative Regimen (Multi-Tablet)

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

Substitutions if needed:

• Tenofovir disoproxil fumarate (TDF) 300mg can replace TAF, though TAF is preferred for better renal and bone safety 3
• Lamivudine (3TC) 300mg can replace emtricitabine 3

Outdated Regimens to Avoid

The 2001 guidelines recommended zidovudine (AZT) + lamivudine (3TC) as the basic regimen, with expanded regimens adding protease inhibitors like indinavir or nelfinavir. 4 These older regimens are now obsolete—the 2025 CDC guidelines supersede these recommendations with integrase inhibitor-based regimens that have superior efficacy, tolerability, and adherence profiles. 1, 2, 3

Baseline Assessment and Testing

Before administering the first PEP dose (but without delaying it):

• Rapid or laboratory-based HIV antigen/antibody combination test 1, 2
• Baseline renal function (creatinine, eGFR) before any tenofovir-based regimen 1, 3
• Current medications review for potential drug interactions 2, 3
• Medical comorbidities and allergies assessment 2

Special consideration: If the exposed person received long-acting injectable PrEP in the past 12 months, add an HIV nucleic acid test (NAT) to the baseline testing. 2, 3

Follow-Up Testing Schedule

Early Follow-Up (Within 72 Hours)

• Evaluate the exposed person within 72 hours after starting PEP 3
• Monitor for drug toxicity for at least 2 weeks 4, 3
• Provide adherence support and address any side effects 2

Interim Testing (4-6 Weeks Post-Exposure)

• HIV antigen/antibody test PLUS HIV nucleic acid test (NAT) 2, 3

Final Testing (12 Weeks Post-Exposure)

• Laboratory-based HIV antigen/antibody combination immunoassay AND HIV nucleic acid test (NAT) 2, 3

The older 2001 guidelines recommended testing at baseline, 6 weeks, 3 months, and 6 months. 4 The current 2025 guidelines have streamlined this to baseline, 4-6 weeks, and 12 weeks, which is more practical and evidence-based. 2, 3

Duration and Adherence

Complete the full 28-day course regardless of subsequent information about the source patient. 1, 2, 3 The only exception is if the source is later confirmed to be HIV-negative, in which case PEP can be stopped. 1, 3

Incomplete adherence significantly reduces effectiveness—emphasize this to the exposed healthcare worker. 2, 3

Special Populations and Considerations

Renal Impairment

For patients with impaired renal function, use tenofovir alafenamide (TAF) instead of tenofovir disoproxil fumarate (TDF) due to improved renal safety. 1, 3

Pregnancy

Pregnancy does not preclude the use of optimal PEP regimens and should not be a reason to deny PEP. 4 Expert consultation is advised but should not delay initiation. 4

Drug Resistance Concerns

If the source patient's virus is known or suspected to be resistant to one or more drugs in the standard regimen, select drugs to which the source virus is unlikely to be resistant. 4 However, resistance testing of the source patient's virus at the time of exposure is not recommended. 4

Common Pitfalls to Avoid

Never prescribe only two NRTIs (like tenofovir/emtricitabine alone) for PEP—this provides inadequate protection and requires a third drug (integrase inhibitor). 3

Never delay initiation beyond 72 hours—efficacy drops precipitously after this window. 1, 2, 3

Never use salvage therapy agents (fostemsavir, ibalizumab) for PEP—these are reserved for treatment-experienced patients with documented resistance. 3

Do not stop PEP due to minor side effects like nausea or diarrhea—these can often be managed with antimotility or antiemetic agents without changing the regimen. 4

Counseling and Secondary Transmission Prevention

Advise the exposed person to:

• Use precautions to prevent secondary transmission during the follow-up period (barrier protection during sexual activity, avoid blood/tissue donation) 4
• Seek immediate medical evaluation for any acute illness during follow-up, as this could represent acute retroviral syndrome 4
• Report any symptoms of drug toxicity promptly 4, 2

Expert Consultation Resources

For complex cases (delayed presentation, unknown source, pregnancy, suspected drug resistance, or significant toxicity), contact the National Clinicians' Post-Exposure Prophylaxis Hotline (PEPline) at 1-888-448-4911. 4, 1 However, do not delay PEP initiation while awaiting consultation. 1, 3

Transition to PrEP After Completing PEP

For healthcare workers with anticipated repeat or ongoing HIV exposure risk, consider immediate transition from PEP to pre-exposure prophylaxis (PrEP) after completing the 28-day course. 2, 3 Perform HIV testing at completion of PEP before transitioning to PrEP. 2, 3