What is the recommended protocol for post-exposure HIV (Human Immunodeficiency Virus) testing and prophylaxis?

Post-Exposure HIV Testing Protocol

Initiate post-exposure prophylaxis (PEP) immediately without waiting for test results, and perform final conclusive HIV testing at 12 weeks post-exposure using both fourth-generation antigen/antibody testing and nucleic acid testing (NAT). 1, 2

Immediate Actions (Within 72 Hours)

Baseline Testing at Initial Visit

• Perform rapid HIV antibody or rapid antigen/antibody test at the point of care to rule out pre-existing infection 1
• Add a laboratory-based fourth-generation antigen/antibody (Ag/Ab) test to increase sensitivity for HIV detection 1, 2
• For persons with long-acting injectable PrEP exposure in the past 12 months: Add diagnostic HIV nucleic acid testing (NAT) at baseline in addition to Ag/Ab testing 1
• Do not delay PEP initiation pending any test results or source person assessment 1, 2

Source Person Testing

• Test source person with fourth-generation HIV antigen/antibody test when possible, as it detects infection several weeks earlier than standard antibody tests 1
• If source tests negative and has no clinical signs of acute HIV infection, PEP is not indicated 1
• Do not test discarded needles or syringes for virus contamination 1

PEP Regimen

Preferred Medications (28-Day Course)

First-line options for adults and adolescents: 1

• Bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF), OR
• Dolutegravir (DTG) plus (tenofovir alafenamide [TAF] OR tenofovir disoproxil fumarate [TDF]) plus (emtricitabine [FTC] OR lamivudine [3TC])

The CDC 2025 guidelines prioritize these integrase inhibitor-based regimens over older zidovudine-based regimens due to better tolerability and adherence 1, though the 2001 guidelines listed zidovudine combinations as basic regimens 1.

Follow-Up Testing Schedule

Interim Testing at 4-6 Weeks

• Perform both laboratory-based HIV Ag/Ab test AND diagnostic HIV NAT 1, 2
• Exception: This may be deferred for persons who started PEP within 24 hours of exposure and did not miss any doses 1, 2

Final Testing at 12 Weeks Post-Exposure

• Perform both laboratory-based HIV Ag/Ab combination immunoassay AND diagnostic HIV NAT 1, 2
• This 12-week timepoint is considered conclusive by the CDC, accounting for antiretroviral medication washout and the window period for HIV tests 2
• The combination of both tests at 12 weeks provides definitive results 1, 2

Critical Pitfalls to Avoid

Testing Considerations

• Never use oral fluid rapid tests in the PEP context—they are less sensitive for acute/recent infection than blood tests 2
• Antiretroviral medications (PEP or PrEP) can suppress viral load, delay antibody formation, and reduce HIV detection ability 2, 3
• Fourth-generation tests detect infection approximately 2 weeks post-exposure, significantly earlier than older antibody-only tests 4

Clinical Monitoring

• Evaluate persons taking PEP within 72 hours after starting and monitor for drug toxicity for at least 2 weeks 1
• Advise exposed persons to seek immediate medical evaluation for any acute illness during follow-up, as this may indicate acute retroviral syndrome 1
• Counsel on precautions to prevent secondary transmission during the follow-up period 1

Additional Testing

• Test for other sexually transmitted infections at baseline 1
• For hepatitis exposures: Test for HBsAg and anti-HCV at baseline 1

Transition to Prevention

• Offer PrEP to those with anticipated repeat or ongoing potential HIV exposures, with immediate transition from PEP to PrEP after completion of the 28-day course and final HIV testing 1