Praxis Medical Insights

Est. 2024 • Clinical Guidelines Distilled

Made possible by volunteer editors from the University of Calgary & University of Alberta

Last Updated: 9/23/2025

Post-Exposure HIV Testing and Prophylaxis Protocol

Immediate Actions (Within 72 Hours)

  • The Centers for Disease Control and Prevention (CDC) recommends initiating post-exposure prophylaxis (PEP) immediately without waiting for test results, and performing final conclusive HIV testing at 12 weeks post-exposure using both fourth-generation antigen/antibody testing and nucleic acid testing (NAT) 1, 2
  • Perform rapid HIV antibody or rapid antigen/antibody test at the point of care to rule out pre-existing infection, and add a laboratory-based fourth-generation antigen/antibody (Ag/Ab) test to increase sensitivity for HIV detection 3, 4, 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 3, 4, 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 3, 4
  • If source tests negative and has no clinical signs of acute HIV infection, PEP is not indicated 3
  • Do not test discarded needles or syringes for virus contamination 5, 6

PEP Regimen

  • The CDC recommends first-line options for adults and adolescents, including 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) 1
  • The CDC prioritizes these integrase inhibitor-based regimens over older zidovudine-based regimens due to better tolerability and adherence 1

Follow-Up Testing Schedule

  • Perform both laboratory-based HIV Ag/Ab test and diagnostic HIV NAT at 4-6 weeks post-exposure, except for persons who started PEP within 24 hours of exposure and did not miss any doses 1, 2
  • Perform both laboratory-based HIV Ag/Ab combination immunoassay and diagnostic HIV NAT at 12 weeks post-exposure, which is considered conclusive by the CDC 1, 2

Critical Pitfalls to Avoid

  • Never use oral fluid rapid tests in the PEP context, as 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

Clinical Monitoring

  • Evaluate persons taking PEP within 72 hours after starting and monitor for drug toxicity for at least 2 weeks 5, 6
  • Advise exposed persons to seek immediate medical evaluation for any acute illness during follow-up, as this may indicate acute retroviral syndrome 5, 6
  • Counsel on precautions to prevent secondary transmission during the follow-up period 5, 6

Additional Testing

  • Test for other sexually transmitted infections at baseline 3, 4
  • For hepatitis exposures, test for HBsAg and anti-HCV at baseline 5, 6

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