What labs are needed to restart Pre-Exposure Prophylaxis (PrEP) after a 2-year hiatus?

Laboratory Testing for Restarting PrEP After 2-Year Hiatus

When restarting PrEP after a 2-year hiatus, you must obtain HIV testing (both a fourth- or fifth-generation laboratory-based antigen-antibody test AND an HIV RNA test with lower limit of quantification ≤50 copies/mL), serum creatinine with calculated creatinine clearance, hepatitis B surface antigen, and STI screening before reinitiating medication. 1

Mandatory HIV Testing Before Restart

The 2025 International Antiviral Society-USA guidelines are explicit that after a hiatus exceeding 14 days for tenofovir-based oral PrEP (or 6 months for long-acting cabotegravir), HIV screening should ideally include both an HIV RNA test and a laboratory-based antigen-antibody test before restarting. 1

• HIV RNA (viral load) test with 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
• Fourth- or fifth-generation laboratory-based antigen-antibody test must be performed concurrently. 1, 2
• If HIV RNA testing is unavailable or not feasible, you can still restart PrEP after a rapid point-of-care HIV antibody test while awaiting the laboratory-based antigen/antibody test results, but this is a compromise approach. 1
• Critical pitfall: Starting PrEP during undiagnosed acute HIV infection can lead to drug resistance, particularly M184V/I mutations. 2

Essential Renal Function Assessment

Since this patient has been off PrEP for 2 years, baseline renal function must be reassessed before restarting:

• Serum creatinine with calculated creatinine clearance (CrCl) is mandatory. 1, 2
• TDF-based PrEP is contraindicated if CrCl <60 mL/min. 2, 3
• Use the Cockcroft-Gault formula for calculation. 1

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. 2, 3
• This is particularly important after a 2-year gap, as the patient's HBV status may have changed. 2

Additional Baseline Testing

Before restarting PrEP, also obtain:

• Hepatitis C antibody testing (if not previously positive or if status unknown). 1, 2
• STI screening by nucleic acid amplification test (NAAT) for Neisseria gonorrhoeae and Chlamydia trachomatis from all exposure sites (genital, rectal, pharyngeal based on sexual practices). 1, 2
• Syphilis serology. 1, 2
• Pregnancy testing for individuals of childbearing potential. 1, 2
• Hepatitis A IgG antibody for men who have sex with men and people who inject drugs (if not known to be immune). 1, 2

Timing Considerations for Restart

If HIV test results from within the past 7 days are negative, you can initiate PrEP while awaiting further diagnostics and safety assessments. 1 However, given the 2-year hiatus, fresh testing is strongly recommended. 1

Follow-Up Testing After Restart

Once PrEP is restarted, the monitoring schedule resets:

• At 1 month: Repeat HIV antigen-antibody test to catch any breakthrough infections early. 1, 2
• Every 3 months (quarterly): HIV antigen-antibody testing, STI screening (gonorrhea, chlamydia, syphilis), and pregnancy testing if applicable. 1, 2
• Creatinine clearance: At first quarterly visit, then annually (or every 3-6 months if patient has risk factors like age >50, baseline CrCl <90 mL/min, diabetes, or hypertension). 1, 2

Common Pitfalls to Avoid

• Do not skip HIV RNA testing if available—the 2-year gap represents substantial time for potential HIV exposure, and acute infection must be ruled out definitively. 1
• Do not restart PrEP with only a rapid antibody test—this misses acute HIV infection and risks creating drug resistance. 1, 2
• Do not forget hepatitis B testing—abrupt discontinuation of tenofovir in HBV-positive patients can be life-threatening. 2, 3
• Do not assume prior renal function is still normal—2 years is sufficient time for renal status to change. 2