What is the recommended monitoring and management approach for a patient on prep treatment to prevent HIV infection and minimize side effects, considering their kidney function and potential history of kidney disease?

PrEP Treatment Monitoring

Patients on PrEP require combined HIV antibody/antigen testing at 1 month, then quarterly, with creatinine clearance monitoring at the first quarterly visit and annually thereafter (or every 3-6 months for those at increased kidney risk), plus quarterly STI screening and syphilis testing. 1

Pre-Initiation Testing Requirements

Before starting PrEP, the following tests are mandatory:

• Combined HIV antibody/antigen test (4th generation) must be negative before initiating PrEP 1, 2

  • If clinical suspicion of acute HIV exists (fever, rash, lymphadenopathy, pharyngitis), add HIV RNA testing and withhold PrEP until results confirm negative status 1, 2
  • Initiating PrEP during undiagnosed acute HIV can lead to drug resistance, particularly M184V/I mutations 2

• Serum creatinine with calculated creatinine clearance is required, but PrEP should not be delayed while waiting for results—only HIV testing should gate initiation 1, 2

  • TDF-based PrEP is contraindicated if creatinine clearance <60 mL/min 2, 3

• Hepatitis B surface antigen (HBsAg) testing is essential because stopping TDF in HBV-positive patients can cause severe hepatitis flares or hepatic decompensation 1, 2

• Hepatitis C IgG antibody testing if not previously known to be positive 1, 2

• Hepatitis A IgG antibody for MSM and people who inject drugs if not known to be immune 1, 2

• Genital and nongenital gonorrhea and chlamydia testing by NAAT from all exposure sites (rectal, pharyngeal, urogenital) 1, 2, 3

• Syphilis serology 1, 2

• Pregnancy testing for individuals of childbearing potential 1, 2

Monitoring Schedule During PrEP

At 1 Month After Initiation

• Combined HIV antibody/antigen test to catch any breakthrough infections early 1, 2

Quarterly (Every 3 Months)

• Combined HIV antibody/antigen test 1, 2, 3

• Estimated creatinine clearance at the first quarterly visit, then annually thereafter 1, 2

  • More frequent monitoring every 3-6 months is required for patients at increased risk of kidney injury: age >50 years, baseline creatinine clearance <90 mL/min, diabetes, hypertension, or chronic kidney disease 1, 2, 3
  • Also assess serum phosphorus in patients with chronic kidney disease 4
  • Assess urine glucose and urine protein on a clinically appropriate schedule 4

• Genital and nongenital gonorrhea and chlamydia testing by NAAT from all potentially exposed anatomic sites 1, 2, 3

• Syphilis testing 1, 2

• Pregnancy testing for individuals of childbearing potential 1, 2

Annually

• Combined HIV antibody/antigen test 1, 2

• Estimated creatinine clearance if not being monitored more frequently 1, 2

• Hepatitis C antibody testing 1, 2

  • Every 3-6 months for people who inject drugs and MSM who use recreational drugs at the time of sex if liver function test results are abnormal 1, 2

Management of Kidney Function Changes

Expected Creatinine Changes on TDF-Based PrEP

Small, nonprogressive decreases in creatinine clearance are expected with TDF/FTC PrEP:

• Mean creatinine increases by approximately 0.03 mg/dL (4.6%) and creatinine clearance decreases by approximately 4.8 mL/min (3.0%) at week 12, remaining stable thereafter 5, 6
• These changes are typically reversible after stopping PrEP 6
• Approximately 23% of participants may experience reductions in eGFR greater than 10 mL/min/1.73 m² at week 4, but these are generally nonprogressive 7

Management Algorithm for Mild Creatinine Elevation

For patients with mild creatinine elevation but creatinine clearance remaining >60 mL/min:

• Reassure the patient that the creatinine increase is typically transient and expected 2
• Check for proteinuria today to allow early detection of rare cases requiring intervention 2
• Recheck kidney function in 1-3 months 2
• Increase monitoring frequency to every 3 months going forward, as the patient now has a risk factor for kidney changes 2
• Do not discontinue PrEP based solely on mild creatinine elevation with creatinine clearance >60 mL/min—this represents an overreaction to expected pharmacologic effects 2
• Do not refer to nephrology at this stage unless proteinuria is significant or creatinine clearance continues declining below 60 mL/min on repeat testing 2

When to Switch from TDF to TAF

For MSM with or at risk for kidney dysfunction, osteopenia, or osteoporosis, switch to daily tenofovir alafenamide/emtricitabine (Descovy) 1, 3

• TAF has less impact on renal function compared to TDF 1
• Critical limitation: TAF (Descovy) is NOT recommended for cisgender women or event-driven "2-1-1" dosing 3

When to Discontinue PrEP for Renal Concerns

• Discontinue TDF-based PrEP if creatinine clearance falls below 60 mL/min 2, 3
• Consider switching to TAF if creatinine clearance is 30-60 mL/min in MSM 3

Special Monitoring Considerations

Patients with Chronic Kidney Disease

• Assess serum phosphorus in addition to creatinine, creatinine clearance, urine glucose, and urine protein on a clinically appropriate schedule 4
• TDF-based PrEP is contraindicated if creatinine clearance <60 mL/min 2, 3
• TAF is not recommended if creatinine clearance <15 mL/min unless on chronic hemodialysis 4

Patients with Hepatitis B Co-infection

• Additional monitoring is required when stopping agents active against HBV (tenofovir, emtricitabine, lamivudine) 1
• Risk of severe hepatitis flare or hepatic decompensation exists if tenofovir is discontinued, particularly in patients with cirrhosis 1, 3, 8
• Hepatic function should be monitored closely for several months after discontinuation 4

If PrEP is Restarted After Interruption

• If PrEP is stopped for ≥7 consecutive days, repeat combined HIV antibody/antigen testing before restarting 2

If HIV Infection is Suspected While on PrEP

• Order immediate HIV RNA and genotype testing 2, 3
• Add a boosted protease inhibitor (ritonavir-boosted darunavir) and/or dolutegravir to the TDF/emtricitabine pending results 2, 3
• Switch to a recommended initial antiretroviral regimen once HIV is confirmed 3

If Substantial Nonadherence with High-Risk Exposure Occurs

• Discontinue PrEP and initiate 28-day course of 3-drug PEP instead 2

Common Pitfalls to Avoid

• Do not delay PrEP initiation while waiting for creatinine results—only HIV testing should gate initiation 2
• Do not discontinue PrEP based solely on mild creatinine elevation with creatinine clearance >60 mL/min 2
• Do not forget to monitor for proteinuria in addition to creatinine clearance 2, 4
• Do not abruptly stop tenofovir-containing regimens in patients with hepatitis B without close hepatic function monitoring 1, 3, 8, 4
• Do not prescribe TAF (Descovy) for cisgender women or for event-driven dosing—it is only indicated for MSM with specific renal or bone concerns 3