What is the recommended post-exposure prophylaxis (PEP) regimen for a previously vaccinated adult with no significant medical history, who has been exposed to Human Immunodeficiency Virus (HIV)?

Post-Exposure Prophylaxis for HIV in Previously Vaccinated Persons

For a previously vaccinated adult exposed to HIV, initiate bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) as a single tablet once daily for 28 days, starting as soon as possible within 72 hours of exposure. 1, 2

Critical Timing

• Start PEP immediately, ideally within 24 hours of exposure, but no later than 72 hours maximum 1, 2
• Do not delay the first dose while awaiting laboratory results or source patient testing 3, 2
• Efficacy decreases significantly with delayed initiation 1, 2
• If the source is confirmed HIV-negative during the 28-day course, PEP can be stopped 2

Preferred Regimen (First-Line)

Bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF):

• Single tablet once daily for 28 days 1, 2
• Bictegravir 50mg/emtricitabine 200mg/tenofovir alafenamide 25mg 2
• This is the CDC's preferred regimen due to superior tolerability, completion rates, and fewer drug-drug interactions 1, 4

Alternative Preferred Regimen

Dolutegravir (DTG) 50mg once daily PLUS emtricitabine/tenofovir alafenamide (FTC/TAF) 200mg/25mg once daily:

• Multi-tablet regimen for 28 days 1, 2
• Can substitute tenofovir disoproxil fumarate (TDF) 300mg for TAF if TAF is unavailable, though TAF is preferred for better renal and bone safety 2
• Can substitute lamivudine (3TC) 300mg for emtricitabine if needed 2

Baseline Assessment Before Starting PEP

Immediate testing (do not delay PEP initiation):

• Rapid or laboratory-based HIV antigen/antibody combination test 1, 2
• Add HIV nucleic acid test (NAT) if the patient received long-acting injectable PrEP in the past 12 months 2
• Assess baseline renal function before initiating any tenofovir-based regimen 1, 2
• Evaluate current medications, allergies, and medical comorbidities for potential drug interactions 2

Special Populations

Renal impairment:

• Use tenofovir alafenamide (TAF) instead of tenofovir disoproxil fumarate (TDF) for patients with impaired renal function 1, 2
• TAF may be considered for individuals with creatinine clearance between 30-60 mL/min or with known bone density issues 5

Pregnant healthcare workers:

• The older regimen of zidovudine (ZDV) plus lamivudine (3TC), available as Combivir, is considered safe 3, 5
• This regimen has been used more extensively in pregnancy and has predictable, manageable side effects 3

Follow-Up Testing Schedule

Within 72 hours after starting PEP:

• Evaluate the exposed person and monitor for drug toxicity for at least 2 weeks 3, 2, 5

At 4-6 weeks:

• HIV antigen/antibody test plus HIV NAT 2

At 12 weeks (3 months):

• Laboratory-based HIV antigen/antibody combination immunoassay and HIV NAT 2

At 6 months:

• Final HIV antibody testing to confirm no seroconversion 3, 5

During follow-up period:

• Advise exposed persons to use precautions to prevent secondary transmission 3, 5
• Seek immediate medical evaluation for any acute illness compatible with acute retroviral syndrome 3, 5

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) 1, 2
• Three-drug therapy is now favored for all potential HIV exposures 3, 4

Never use salvage therapy agents for PEP:

• Fostemsavir and ibalizumab are reserved for treatment-experienced patients with documented resistance, not for PEP 1, 2

Never delay initiation beyond 72 hours:

• Effectiveness drops significantly after this window 1, 2

Assess for drug interactions:

• Evaluate potential interactions with concurrent medications before prescribing 2
• Consider different regimens if the patient has a history of antiretroviral exposure 2

Adherence and Completion

• Complete the full 28-day course regardless of which regimen is used 3, 2, 5
• Incomplete adherence significantly reduces effectiveness 2
• Newer regimens (BIC/FTC/TAF or DTG-based) have better tolerability and completion rates compared to older zidovudine-based regimens 4

Transition to PrEP After Completing PEP

For persons with anticipated repeat or ongoing HIV exposures:

• Consider immediate transition from PEP to PrEP 1, 2
• Perform HIV testing at completion of the 28-day PEP course before transitioning to PrEP 1, 2
• PEP can be viewed as an educable moment and a potential bridge to preexposure prophylaxis as part of a combination prevention package 4

Note on "Previously Vaccinated" Status

There is no HIV vaccine currently available for clinical use. If the question refers to vaccination against other bloodborne pathogens (HBV, HCV), this does not change HIV PEP recommendations. For HBV exposure in a previously vaccinated person, follow-up anti-HBs testing should be performed 1-2 months after the last vaccine dose 3. For HCV exposure, PEP is not recommended regardless of vaccination status 3.