Praxis Medical Insights

Est. 2024 • Clinical Guidelines Distilled

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

Last Updated: 11/11/2025

Laboratory Testing for Restarting PrEP After a 2-Year Hiatus

Mandatory HIV Testing Before Restart

  • The International Antiviral Society-USA guidelines recommend that HIV screening should ideally include both an HIV RNA test and a laboratory-based antigen-antibody test before restarting PrEP after a hiatus exceeding 14 days for tenofovir-based oral PrEP 1, 2, 3.
  • An HIV RNA (viral load) test with a lower limit of quantification of 50 copies/mL or lower is the gold standard for detecting acute HIV infection that antibody/antigen tests might miss 1, 2.
  • A fourth- or fifth-generation laboratory-based antigen-antibody test must be performed concurrently 1, 2, 4.

Essential Renal Function Assessment

  • Baseline renal function must be reassessed before restarting PrEP, including serum creatinine with calculated creatinine clearance (CrCl) 5, 4.
  • The Cockcroft-Gault formula should be used for calculation 5.

Hepatitis B Testing

  • Hepatitis B surface antigen (HBsAg) testing is essential because stopping tenofovir-based PrEP in HBV-positive patients can cause severe hepatitis flares, liver decompensation, and liver failure 4.

Additional Baseline Testing

  • Hepatitis C antibody testing should be performed if not previously positive or if status unknown 6, 4.
  • STI screening by nucleic acid amplification test (NAAT) for Neisseria gonorrhoeae and Chlamydia trachomatis from all exposure sites should be performed 5, 6, 4.
  • Syphilis serology should be performed 6, 4.
  • Pregnancy testing should be performed for individuals of childbearing potential 5, 6, 4.
  • Hepatitis A IgG antibody testing should be performed for men who have sex with men and people who inject drugs (if not known to be immune) 6, 4.

Timing Considerations for Restart

  • If HIV test results from within the past 7 days are negative, PrEP can be initiated while awaiting further diagnostics and safety assessments 7.

Follow-Up Testing After Restart

  • At 1 month, repeat HIV antigen-antibody test to catch any breakthrough infections early 2, 6, 4.
  • Every 3 months (quarterly), HIV antigen-antibody testing, STI screening (gonorrhea, chlamydia, syphilis), and pregnancy testing if applicable should be performed 6, 4.
  • Creatinine clearance should be checked at first quarterly visit, then annually (or every 3-6 months if patient has risk factors) 6, 4.

Common Pitfalls to Avoid

  • Do not skip HIV RNA testing if available, as the 2-year gap represents substantial time for potential HIV exposure, and acute infection must be ruled out definitively 1, 2.
  • Do not restart PrEP with only a rapid antibody test, as this misses acute HIV infection and risks creating drug resistance 1, 4.
  • Do not forget hepatitis B testing, as abrupt discontinuation of tenofovir in HBV-positive patients can be life-threatening 4.
  • Do not assume prior renal function is still normal, as 2 years is sufficient time for renal status to change 4.