What are safe HIV Pre-Exposure Prophylaxis (PrEP) medications for a patient with impaired renal function (kidney disease)?

HIV PrEP Medications Safe for Patients with Kidney Disease

For patients with kidney disease requiring HIV PrEP, tenofovir alafenamide/emtricitabine (TAF/FTC) is the preferred option for those with creatinine clearance ≥30 mL/min, while injectable cabotegravir represents the safest alternative for those with more severe renal impairment or contraindications to tenofovir formulations. 1

Primary Recommendation: Tenofovir Alafenamide-Based PrEP

For men who have sex with men (MSM) with or at risk for kidney dysfunction, daily tenofovir alafenamide/emtricitabine (TAF/FTC) is specifically recommended over tenofovir disoproxil fumarate (TDF). 1 This represents the most direct guideline-based answer for PrEP in renal impairment.

Key Advantages of TAF/FTC:

• TAF achieves 90% lower plasma tenofovir concentrations compared to TDF, resulting in substantially reduced renal tubular exposure and nephrotoxicity risk. 1, 2
• Clinical trials demonstrate that TAF is well tolerated in patients with mild to moderate renal impairment (CrCl >30 mL/min) without dose adjustment. 3
• Switching from TDF to TAF results in significant improvements in proteinuria, albuminuria, and tubular proteinuria markers. 3

Critical Renal Function Thresholds:

TAF/FTC should NOT be used when creatinine clearance falls below 30 mL/min. 1, 4 The FDA label explicitly states that TAF lacks established safety data below this threshold, and pharmacokinetic studies show dramatically elevated tenofovir exposures in end-stage renal disease (ESRD). 4

• For CrCl 30-60 mL/min: TAF/FTC can be used at standard dosing (25 mg TAF/200 mg FTC daily) without adjustment. 5, 4
• For CrCl <30 mL/min: TAF/FTC is contraindicated for PrEP use; alternative strategies are required. 5

Alternative Option: Injectable Cabotegravir

Injectable cabotegravir every 8 weeks is recommended as PrEP for cisgender men and transgender women who have sex with men and represents the optimal choice for patients with significant renal impairment. 1

Advantages in Renal Disease:

• Cabotegravir does not require renal dose adjustment and is not nephrotoxic, making it ideal for patients with any degree of kidney dysfunction. 1
• Eliminates concerns about tenofovir-related proximal tubular dysfunction, Fanconi syndrome, and progressive eGFR decline. 1
• Provides superior adherence through long-acting formulation, particularly valuable in patients with complex medication regimens due to comorbidities. 1

Why TDF/FTC Should Be Avoided

Tenofovir disoproxil fumarate (TDF) should be avoided or dose-adjusted in patients with creatinine clearance below 60 mL/min. 1

Specific Nephrotoxicity Concerns:

• TDF causes cumulative nephrotoxicity with 1-2% developing treatment-limiting tubulopathy, manifesting as proximal tubular dysfunction with glycosuria, phosphaturia, proteinuria, and metabolic acidosis. 1, 6
• Risk factors that amplify TDF nephrotoxicity include aging, immunodeficiency, diabetes, prolonged exposure, and concomitant use of ritonavir-boosted protease inhibitors. 1
• TDF requires dose adjustment to every 48 hours when CrCl is 30-49 mL/min, and should be discontinued if CrCl drops below 30 mL/min. 7

Monitoring Requirements for PrEP in Renal Disease

Pre-Initiation Assessment:

• Serum creatinine with calculated creatinine clearance (Cockcroft-Gault) is mandatory before starting any PrEP regimen. 1
• Combined HIV antibody and antigen testing to exclude acute HIV infection. 1
• Hepatitis B surface antigen testing (critical because discontinuing tenofovir in HBV-positive patients can cause severe hepatitis flares). 1

During PrEP Use:

• For patients with or at risk for kidney injury, estimated creatinine clearance should be monitored every 3-6 months rather than annually. 1, 5
• Urinalysis for proteinuria and glycosuria to detect early proximal tubular dysfunction. 5, 6
• If eGFR drops by >25% from baseline and decreases to <60 mL/min/1.73 m², tenofovir-based PrEP should be discontinued. 6

Common Pitfalls and How to Avoid Them

Pitfall #1: Using Standard TDF/FTC in Mild Renal Impairment

Even with CrCl 50-60 mL/min, TDF carries progressive nephrotoxicity risk. 1, 8 Switch to TAF/FTC or cabotegravir rather than continuing TDF with dose adjustment. 1

Pitfall #2: Continuing TAF Below CrCl 30 mL/min

TAF results in very high tenofovir exposures in ESRD, with AUC increasing 55-fold compared to normal renal function. 4, 2 Despite some case reports of use in hemodialysis patients, this is off-label and lacks safety data for PrEP. 9

Pitfall #3: Ignoring Nephrotoxic Drug Interactions

Concurrent use of NSAIDs, aminoglycosides, or other nephrotoxic agents with tenofovir-based PrEP dramatically increases acute kidney injury risk. 5, 7 Cases of acute renal failure requiring hospitalization and dialysis have been reported with this combination. 7

Pitfall #4: Inadequate Monitoring Frequency

Standard quarterly monitoring is insufficient for patients with baseline renal impairment; these patients require creatinine assessment every 3 months at minimum. 1, 5

Pitfall #5: Misinterpreting Small Creatinine Changes

Mean creatinine increases of 0.03 mg/dL (4.6%) and CrCl decreases of 4.8 mL/min occur within the first 12 weeks of TDF/FTC PrEP and typically stabilize thereafter. 8 However, these changes warrant closer monitoring rather than dismissal, particularly in patients with baseline CrCl <90 mL/min. 8

Algorithm for PrEP Selection in Kidney Disease

Step 1: Calculate baseline creatinine clearance (Cockcroft-Gault method)

• CrCl ≥60 mL/min: TAF/FTC is preferred over TDF/FTC for long-term renal safety. 1
• CrCl 30-59 mL/min: TAF/FTC at standard dosing OR injectable cabotegravir (preferred if available). 1, 5, 4
• CrCl <30 mL/min: Injectable cabotegravir is the only appropriate option; tenofovir formulations are contraindicated. 5, 4

Step 2: Assess additional risk factors

• If diabetes, hypertension, age >40 years, or concurrent nephrotoxic medications: Strongly favor injectable cabotegravir over any tenofovir formulation. 1, 5, 8
• If osteopenia or osteoporosis: TAF/FTC is preferred over TDF/FTC, but cabotegravir eliminates bone concerns entirely. 1

Step 3: Implement appropriate monitoring schedule

• CrCl >60 mL/min: Quarterly HIV testing, annual creatinine clearance. 1
• CrCl 30-60 mL/min: Quarterly HIV testing, creatinine clearance every 3-6 months, urinalysis for proteinuria/glycosuria every 6 months. 1, 5