What are the recommended testing guidelines and post-exposure prophylaxis (PEP) regimen for an individual with potential human immunodeficiency virus (HIV) exposure?

HIV Post-Exposure Testing and Prophylaxis Guidelines

Initiate post-exposure prophylaxis (PEP) immediately—ideally within 24 hours and no later than 72 hours after exposure—using a three-drug antiretroviral regimen, with bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) as the first-line choice. 1

Immediate Assessment and PEP Initiation

Baseline Testing Requirements

• Perform rapid HIV antibody or antigen-antibody combination test on the exposed person immediately to rule out pre-existing infection 2
• Add HIV nucleic acid test (NAT) if the patient received long-acting injectable PrEP within the past 12 months 1
• Do not delay PEP initiation while waiting for test results—assume the exposed person is HIV-negative and start treatment immediately 2
• Test the source person using a fourth-generation HIV antigen-antibody test when possible, as this detects infection earlier than standard antibody tests 2

Exposures Warranting PEP

PEP is indicated for exposures to potentially infectious fluids including 2:

• Blood and blood-stained saliva
• Semen, vaginal secretions, rectal secretions
• Breast milk
• Cerebrospinal, amniotic, peritoneal, synovial, pericardial, or pleural fluids
• Via mucous membrane (sexual exposure, splashes to eye/nose/mouth) or parenteral routes

Exposures NOT Requiring PEP

Do not initiate PEP when 2:

• The exposed person is already HIV-positive
• The source is confirmed HIV-negative
• Exposure involves non-infectious fluids: tears, non-bloody saliva, urine, feces, vomitus, sputum, nasal secretions, sweat

Recommended PEP Regimens

First-Line Regimen

Bictegravir 50mg/emtricitabine 200mg/tenofovir alafenamide 25mg (BIC/FTC/TAF) once daily for 28 days 1

• This single-tablet regimen offers superior renal and bone safety compared to older regimens and improves adherence 1

Alternative Regimen

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

• Tenofovir disoproxil fumarate (TDF) 300mg may substitute for TAF if unavailable, though TAF is preferred for renal safety 1

Critical Timing

• The 72-hour window is absolute—efficacy decreases dramatically with each passing hour 1
• Complete the full 28-day course regardless of subsequent information about the source patient 1
• Incomplete adherence significantly reduces effectiveness 1

Follow-Up Testing Schedule

Using Fourth-Generation Combination Tests (Preferred)

When using newer fourth-generation HIV p24 antigen-antibody combination tests, the CDC recommends 3, 1, 4:

• Within 72 hours after starting PEP: Clinical evaluation and drug toxicity assessment 1
• At 4-6 weeks: HIV antigen/antibody test PLUS HIV nucleic acid test (NAT) 1
• At 12 weeks (3 months): Laboratory-based HIV antigen/antibody combination immunoassay AND HIV nucleic acid test (NAT) 1
• Testing may be concluded at 4 months when using fourth-generation tests 4

Using Traditional Antibody-Only Tests

If fourth-generation tests are unavailable, extend follow-up to 3, 4:

• Baseline, 6 weeks, 3 months, and 6 months 3

Extended Follow-Up Situations

• 12-month follow-up is required for healthcare workers who become infected with HCV following exposure to a source coinfected with HIV and HCV 3
• Test immediately if acute retroviral syndrome symptoms develop (fever, rash, lymphadenopathy, pharyngitis), regardless of timeline 3

Special Considerations

Renal Impairment

Use tenofovir alafenamide (TAF) instead of tenofovir disoproxil fumarate (TDF) in patients with impaired renal function 1

Pregnancy

Pregnancy does not preclude optimal PEP regimens and should never be a reason to deny PEP 1

• Expert consultation is advised for pregnant patients 1

Counseling Requirements

• Advise precautions to prevent secondary transmission during the follow-up period (barrier contraception, avoid blood/tissue donation) 1
• Instruct immediate medical evaluation for any acute illness during follow-up, as this may indicate acute retroviral syndrome 1

Additional Testing and Interventions

Concurrent Infections

Test for other sexually transmitted infections at baseline 2

Transition to PrEP

For persons with anticipated repeat or ongoing HIV exposures 1:

• Consider immediate transition from PEP to PrEP after completing the 28-day course
• Perform HIV testing at completion of PEP before transitioning to PrEP 1

Common Pitfalls to Avoid

• Never delay PEP for source testing or risk assessment—the window for efficacy is narrow 2
• Do not use two-drug regimens unless three-drug options are absolutely unavailable; current guidelines recommend three drugs for all exposures 2
• Do not discontinue PEP prematurely even if the source is later found to be HIV-negative; complete the full 28 days once started 1
• Do not assume older adults or younger adolescents are low-risk without proper assessment; screen based on exposure risk, not age alone 5