What is the recommended post-exposure prophylaxis (PEP) regimen for a healthcare worker with potential Human Immunodeficiency Virus (HIV) exposure in a hospital setting?

HIV Post-Exposure Prophylaxis for Healthcare Workers

Initiate bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) as a single tablet once daily for 28 days immediately after occupational HIV exposure, ideally within 1-2 hours but no later than 72 hours post-exposure. 1, 2

Immediate Action Protocol

Start PEP immediately without any delay—do not wait for source patient testing, risk assessment, or baseline laboratory results. 1, 2 Efficacy decreases dramatically with each passing hour after exposure. 1, 3

First Steps (Within Minutes of Exposure):

• Wash wounds and skin with soap and water; flush mucous membranes with water 4
• Administer the first dose of PEP as soon as possible, ideally within 24 hours, with an absolute maximum window of 72 hours 1, 2, 3
• Perform rapid HIV antigen/antibody combination test on the exposed healthcare worker (do not delay PEP while awaiting results) 1, 2

Preferred Medication Regimen

First-line choice: Bictegravir 50mg/emtricitabine 200mg/tenofovir alafenamide 25mg (BIC/FTC/TAF) as one tablet once daily for exactly 28 days. 1, 2, 3 This regimen offers superior renal and bone safety compared to older regimens and improves adherence due to single-tablet dosing. 1, 2

Alternative Regimen:

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

Important Medication Notes:

• Always use three antiretroviral drugs—never prescribe only two NRTIs (like tenofovir/emtricitabine alone) as this provides inadequate protection 3, 5
• For patients with impaired renal function, use tenofovir alafenamide (TAF) instead of tenofovir disoproxil fumarate (TDF) 1, 2, 3
• Review current medications for potential drug interactions before prescribing 1, 2

Baseline Assessment

Perform these tests immediately but do not delay the first PEP dose while awaiting results: 1, 2

• Rapid or laboratory-based HIV antigen/antibody combination test 1, 2, 3
• Add HIV nucleic acid test (NAT) if the patient received long-acting injectable PrEP in the past 12 months 1, 2
• Baseline renal function (creatinine, eGFR) before any tenofovir-based regimen 1, 2
• Test source patient for HIV antibody using rapid testing or fourth-generation antigen-antibody test when possible 2

Critical Duration Requirement

The healthcare worker must complete the full 28-day course regardless of any subsequent information about the source patient. 1, 2 Incomplete adherence significantly reduces effectiveness. 1, 2 There is no option for early discontinuation. 2

Adherence Support:

• Provide anti-emetics or other supportive medications proactively to manage side effects like nausea and fatigue 2
• Schedule follow-up visits or phone check-ins during the 28-day course to encourage adherence 2

Follow-Up Testing Schedule

• Within 72 hours after starting PEP: Clinical evaluation and assessment for drug toxicity 1, 2, 3
• At 4-6 weeks: HIV antigen/antibody test PLUS HIV nucleic acid test (NAT) 1, 2
• At 12 weeks: Laboratory-based HIV antigen/antibody combination immunoassay AND HIV nucleic acid test (NAT) 1, 2
• Immediate testing: If acute retroviral symptoms develop (fever, rash, lymphadenopathy, pharyngitis), regardless of timeline 1, 2

Special Populations

Pregnant Healthcare Workers:

Pregnancy does not preclude the use of optimal PEP regimens and should not be a reason to deny PEP. 1, 3 The older regimen of zidovudine plus lamivudine is considered safe for pregnant healthcare workers, though expert consultation is advised. 1, 3

Renal Impairment:

Use tenofovir alafenamide (TAF) instead of tenofovir disoproxil fumarate (TDF) due to improved renal and bone safety profiles. 1, 2, 3

Counseling Requirements

• Advise the exposed person to use precautions to prevent secondary transmission during the follow-up period (barrier methods during sexual activity, avoid blood/tissue donation) 4, 1, 2
• Instruct the patient to seek immediate medical evaluation for any acute illness during follow-up, as this may indicate acute retroviral syndrome 1, 2

Transition to PrEP After Completing PEP

For healthcare workers with anticipated repeat or ongoing HIV exposures, consider immediate transition from PEP to PrEP after performing HIV testing at completion of the 28-day PEP course. 1, 2, 3

Expert Consultation Resources

For complex cases (known source patient resistance, pregnancy, renal/hepatic impairment, drug interactions), contact the National Clinicians' Post-Exposure Prophylaxis Hotline (PEPline) at 1-888-448-4911, but do not delay PEP initiation while awaiting consultation. 1

Common Pitfalls to Avoid

• Never delay PEP for source testing or risk assessment—start immediately 1, 2, 3
• Never use two-drug regimens unless three-drug options are absolutely unavailable 1, 2, 3
• Never discontinue PEP early based on subsequent source patient information 1, 2
• Never fail to assess for drug interactions with the patient's current medications 1, 2
• Never prescribe salvage therapy agents (fostemsavir, ibalizumab) for PEP, as these are reserved for treatment-experienced patients with documented resistance 3

Note on Older Guidelines:

The 2001 guidelines recommended zidovudine (ZDV) + lamivudine (3TC) as the basic regimen, with expanded regimens including protease inhibitors for high-risk exposures. 4 However, these regimens are now outdated and have been replaced by integrase inhibitor-based regimens (BIC/FTC/TAF or DTG + FTC/TAF) due to superior efficacy, safety, and tolerability profiles. 1, 2, 3