When should an HIV test be done after Post-Exposure Prophylaxis (PEP)?

HIV Testing After Post-Exposure Prophylaxis (PEP)

HIV testing should be performed at 4-6 weeks after starting PEP and again at 12 weeks after starting PEP (8 weeks after completing PEP) using both laboratory-based antigen/antibody tests and nucleic acid tests to definitively rule out HIV infection. 1, 2

Recommended Testing Schedule

Initial Testing

• Baseline HIV testing should be performed before initiating PEP using a rapid or laboratory-based antigen/antibody test 1
• PEP should not be delayed while waiting for test results 1

Follow-up Testing

• First follow-up test: 4-6 weeks after starting PEP (within 2 weeks of completing the 28-day course)

  • Should include both laboratory-based antigen/antibody test AND nucleic acid test (NAT) 1, 2
  • This timing helps identify HIV infection in persons who didn't complete or adhere to PEP 2

• Final follow-up test: 12 weeks after starting PEP (8 weeks after completing PEP)

  • Should include both laboratory-based antigen/antibody test AND nucleic acid test (NAT) 1, 2
  • This timing is based on data about antiretroviral washout time and the window period of HIV tests 1

Rationale for Testing Approach

1. Why both types of tests are needed:

   • Antiretroviral medications taken as PEP can suppress HIV viral load, delay seroconversion, and decrease the ability to detect HIV infection 1, 2
   • Using both laboratory-based Ag/Ab tests and NAT improves sensitivity for detecting HIV infection 1

2. Why oral fluid tests are not recommended:

   • Oral fluid-based rapid HIV tests are less sensitive for detecting acute or recent infection than blood tests 1, 2

Special Considerations

• The 4-6 week test may be omitted for individuals who:

  • Started PEP within 24 hours of exposure
  • Were adherent to the complete 28-day PEP course
  • Are not considering starting PrEP 1, 2

• For patients transitioning to PrEP:

  • The 4-6 week follow-up visit is an appropriate time to assess for PrEP indications 1, 2
  • Patients starting PrEP before the final 12-week HIV test should be counseled about the possibility of false-negative results 2

Historical Context

While older guidelines (2001) recommended HIV testing for at least 6 months post-exposure 1, the most recent CDC recommendations (2025) have shortened this to 12 weeks based on improved understanding of antiretroviral washout times and test window periods 1, 2.

Clinical Implications

• PEP efficacy is high when taken as prescribed, with studies showing extremely low failure rates (0.04%) 3
• Most seroconversions after PEP are due to continued high-risk behavior rather than PEP failure 3
• Adherence to the full 28-day PEP regimen is critical for effectiveness, with studies showing approximately 70% adherence rates 3

By following this testing schedule, clinicians can effectively monitor for HIV infection after PEP while minimizing unnecessary testing and maximizing the likelihood of detecting any potential infections.