What is the appropriate dosing of Tenofovir (tenofovir disoproxil fumarate and tenofovir alafenamide) for adults and children, and how should the dose be adjusted for varying levels of renal function?

Tenofovir Dosing

For adults with normal renal function (CrCl ≥50 mL/min), tenofovir disoproxil fumarate (TDF) is dosed at 300 mg once daily, and tenofovir alafenamide (TAF) is dosed at 25 mg once daily. 1, 2

Adult Dosing by Renal Function

Tenofovir Disoproxil Fumarate (TDF)

Standard dose: 300 mg once daily for CrCl ≥50 mL/min 1, 2

Renal dose adjustments (based on creatinine clearance calculated using ideal body weight):

• CrCl 30-49 mL/min: 300 mg every 48 hours 1, 2
• CrCl 10-29 mL/min: 300 mg every 72-96 hours 1, 2
• CrCl <10 mL/min with hemodialysis: 300 mg once weekly (every 7 days) or after approximately 12 hours of cumulative dialysis, administered after dialysis completion 1, 2
• CrCl <10 mL/min without dialysis: Not indicated 1, 2

Tenofovir Alafenamide (TAF)

Standard dose: 25 mg once daily for CrCl ≥15 mL/min 1

Renal dose adjustments:

• CrCl ≥15 mL/min: 25 mg once daily (no adjustment needed) 1
• CrCl <15 mL/min with hemodialysis: 25 mg once daily (generally once weekly, assuming three hemodialysis sessions per week of approximately 4 hours each; administer after dialysis) 1
• CrCl <15 mL/min without dialysis: Not indicated 1

Pediatric Dosing

Children ≥2 Years with HIV or HBV (≥12 years for HBV)

TDF dosing is weight-based at 8 mg/kg once daily (maximum 300 mg) 2:

• 17 to <22 kg: 150 mg once daily
• 22 to <28 kg: 200 mg once daily
• 28 to <35 kg: 250 mg once daily
• ≥35 kg: 300 mg once daily

Weight should be monitored periodically and dose adjusted accordingly. 2

No pediatric renal dosing data are available for either TDF or TAF in children with renal impairment. 2

Critical Selection Considerations

TAF is strongly preferred over TDF in patients with renal risk factors because TAF causes significantly less renal dysfunction and bone mineral density loss. 1 The 2022 KASL guidelines specifically recommend avoiding TDF in patients with:

• Baseline eGFR <60 mL/min
• Proteinuria or albuminuria (urine albumin:creatinine ratio >30 mg/g)
• Hypophosphatemia (<2.5 mg/dL)
• Uncontrolled diabetes or hypertension
• Osteopenia, osteoporosis, or chronic steroid use 1

In a pivotal 96-week trial, patients with renal risk factors on TDF experienced median eGFR decline of -5.0 mL/min versus -0.3 mL/min with TAF, and bone mineral density decreased -3.29% versus -1.23% respectively. 1

Important caveat: TAF is not recommended when CrCl <15 mL/min without dialysis, whereas TDF can be used (with dose adjustment) down to CrCl 10 mL/min with dialysis. 1 For severe renal impairment (CrCl 10-14 mL/min), TDF with appropriate dose adjustment or entecavir may be more appropriate alternatives.

Monitoring Requirements

Before initiating and during treatment with either formulation, assess:

• Serum creatinine and estimated creatinine clearance
• Urine glucose and protein
• Serum phosphorus (in patients with chronic kidney disease)
• Bone mineral density (particularly for TDF-treated patients) 2