Laboratory Testing for PrEP Initiation and Monitoring

Baseline Testing Before Starting PrEP

• The American Medical Association recommends a combined HIV antibody/antigen test (4th generation) and serum creatinine with calculated creatinine clearance before initiating PrEP, but PrEP should not be delayed while waiting for creatinine results—only HIV testing should gate initiation 1, 2
• A combined HIV antibody/antigen test (4th generation) is mandatory and must be negative before starting PrEP, according to the Centers for Disease Control and Prevention (CDC) 3, 4, 5
• If the test was performed within the past 7 days and is negative with no symptoms of acute HIV, the CDC recommends initiating PrEP immediately 1, 2
• HIV RNA testing should be added if any clinical suspicion of acute HIV infection exists (fever, rash, lymphadenopathy, pharyngitis)—withhold PrEP until RNA results return negative, as suggested by the World Health Organization (WHO) 3, 4, 6
• Initiating PrEP during undiagnosed acute HIV can lead to drug resistance, particularly M184V/I mutations, according to the International Antiviral Society-USA 3
• Serum creatinine with calculated creatinine clearance (CrCl) is recommended by the National Institutes of Health (NIH) 3, 4, 5
• Tenofovir disoproxil fumarate (TDF)-based PrEP is contraindicated if CrCl <60 mL/min, as stated by the FDA 7
• Hepatitis B surface antigen (HBsAg) testing is essential because stopping TDF in HBV-positive patients can cause hepatitis flares, according to the American Association for the Study of Liver Diseases (AASLD) 3, 5
• Hepatitis C antibody testing is recommended by the CDC if not previously positive 4, 5
• Hepatitis A IgG antibody testing is recommended for men who have sex with men (MSM) and people who inject drugs by the Advisory Committee on Immunization Practices (ACIP) 5
• Nucleic acid amplification testing (NAAT) for Neisseria gonorrhoeae and Chlamydia trachomatis from all exposure sites is recommended by the CDC 3, 4, 5
• Syphilis serology testing is recommended by the CDC 3, 5
• Pregnancy testing is recommended for individuals of childbearing potential by the American College of Obstetricians and Gynecologists (ACOG) 4, 5

Ongoing Monitoring While on PrEP

• At 1 month after initiation, a combined HIV antibody/antigen test is recommended by the CDC to catch any breakthrough infections early 4, 5, 6
• Quarterly (every 3 months), the CDC recommends combined HIV antibody/antigen testing, NAAT for gonorrhea and chlamydia, syphilis serology, and pregnancy testing for applicable individuals 3, 4, 5, 6
• Calculate creatinine clearance at the first quarterly visit, then annually thereafter, as recommended by the NIH 4, 6
• Monitor every 3-6 months for patients at increased risk of kidney injury: age >50 years, baseline CrCl <90 mL/min, diabetes, hypertension, according to the National Kidney Foundation (NKF) 4, 6
• Annually, the CDC recommends creatinine clearance testing (if not being monitored more frequently), hepatitis C antibody testing, and hepatitis C testing every 3-6 months for people who inject drugs or MSM who use recreational drugs during sex 4, 5, 6
• If PrEP is stopped for ≥7 consecutive days, repeat combined HIV antibody/antigen testing before restarting, as recommended by the WHO 5
• If substantial nonadherence with high-risk exposure occurs, discontinue PrEP and initiate 28-day course of 3-drug PEP instead, according to the CDC 5
• If HIV infection is suspected while on PrEP, order immediate HIV RNA and genotype testing, and add a boosted protease inhibitor (ritonavir-boosted darunavir) and/or dolutegravir to the TDF/emtricitabine pending results, as recommended by the International Antiviral Society-USA 3, 7

Management of Mild Creatinine Elevation in PrEP Users

Rationale for This Approach

• The American Medical Association recommends reassuring the patient that the creatinine increase can be transient and checking for proteinuria, then rechecking kidney function in 1 to 3 months, for patients with mild creatinine elevation, as this change is typically expected and benign, especially when CrCl remains above 60 mL/min 8

Appropriate PrEP Use

• The FDA and medical guidelines suggest that TDF-based PrEP is only contraindicated when CrCl falls below 60 mL/min, and the FDA label specifies dose adjustment or discontinuation only when CrCl drops to <50 mL/min, not for mild elevations with CrCl >60 mL/min 9, 8

Appropriate Monitoring Schedule Going Forward

• The American Medical Association recommends increasing creatinine monitoring frequency to every 3 months for patients with risk factors for kidney changes, such as mild creatinine elevation, as they now have a risk factor for kidney changes 8

Risk Stratification for Future Monitoring

• The American Medical Association suggests that older individuals (>50 years), those with diabetes, hypertension, or baseline CrCl <90 mL/min require closer monitoring every 3 months, due to their increased risk of developing eGFR <70 mL/min 8

Common Pitfalls to Avoid

• The American Medical Association advises against discontinuing PrEP based solely on mild creatinine elevation with CrCl >60 mL/min, as this represents an overreaction to expected pharmacologic effects, and recommends checking proteinuria today to allow early detection of rare cases requiring intervention 8
• The American Medical Association also advises against referring to nephrology at this stage unless proteinuria is significant or CrCl continues declining below 60 mL/min on repeat testing, and recommends a more nuanced approach to monitoring and intervention 8