Switching from Tenofovir to Zidovudine in Renal Impairment
The switch from tenofovir to zidovudine (AZT) plus lamivudine with dolutegravir is appropriate and necessary for this patient with a creatinine clearance of 30 mL/min, as tenofovir poses significant nephrotoxicity risk at this level of renal function and should be discontinued. 1
Why This Switch Was Clinically Indicated
Tenofovir Nephrotoxicity at CrCl 30 mL/min
Tenofovir disoproxil fumarate (TDF) at 300 mg requires dose adjustment to every 48 hours when creatinine clearance is 30-49 mL/min, and patients with preexisting renal dysfunction are at substantially higher risk of further nephrotoxicity. 1
The Infectious Diseases Society of America guidelines recommend discontinuing tenofovir in patients who develop reduced GFR to a level <60 mL/min/1.73 m², particularly when there is evidence of proximal tubular dysfunction. 1
Patients with moderate renal dysfunction (30-59 mL/min) have a 15-fold increased risk of nephrotoxicity compared to those with normal renal function when receiving tenofovir. 2
Tenofovir can cause proximal tubulopathy manifesting as Fanconi syndrome with hypophosphatemia, proteinuria, and normoglycemic glycosuria, which may be exacerbated in patients with preexisting renal impairment. 3, 4
Appropriate Alternative Regimen Components
Zidovudine (AZT) does not require renal dose adjustment and is therefore an appropriate NRTI backbone replacement for tenofovir in patients with significant renal impairment. 1
Lamivudine requires dose adjustment at CrCl 30 mL/min: the standard dose should be reduced from 300 mg daily to 150 mg once daily for creatinine clearance 30-49 mL/min. 1, 5
Dolutegravir 50 mg daily does not require dose adjustment for renal impairment and can be continued at standard dosing. 5, 6
- Note that dolutegravir blocks tubular creatinine secretion, causing approximately a 10% increase in measured serum creatinine without affecting true glomerular filtration rate—this is a benign pharmacologic effect, not true kidney injury. 5, 6
Critical Monitoring Considerations
Verify Correct Lamivudine Dosing
Confirm that the lamivudine component of the combination pill is dosed at 150 mg (not 300 mg) for this patient's creatinine clearance of 30 mL/min. 1, 5
- Most fixed-dose combination tablets are contraindicated when GFR falls below 50 mL/min, requiring individual component dosing with appropriate adjustments. 5
Ongoing Renal Function Monitoring
Monitor creatinine clearance regularly (at least every 3-6 months) as the patient is near the threshold where further dose adjustments would be needed. 5
- If creatinine clearance falls below 30 mL/min, lamivudine dose must be further reduced to 150 mg first dose, then 100 mg once daily for CrCl 15-29 mL/min. 1
Assess for Tenofovir-Related Tubular Damage
Check for signs of proximal tubular dysfunction that may have occurred during tenofovir therapy: urinalysis for proteinuria and glycosuria, serum phosphate levels, and urine protein-to-creatinine ratio. 3, 7
- If tubular dysfunction is present, renal function may improve after tenofovir discontinuation, typically within 4 months. 4
Alternative Considerations
Why Not Other Options?
Tenofovir alafenamide (TAF) could theoretically be used at CrCl 30 mL/min (it's approved down to CrCl >30 mL/min), but given that this patient is already at the lower threshold and TAF is contraindicated below 30 mL/min, the switch away from all tenofovir formulations is more prudent. 1, 5
Abacavir does not require renal dose adjustment and could be an alternative to zidovudine, but requires HLA-B*5701 testing if not previously done, and has potential cardiovascular concerns in patients with CKD. 1
The dual therapy regimen of dolutegravir plus lamivudine (dose-adjusted) without any second NRTI has shown efficacy in suppressed patients with renal impairment and could be considered if zidovudine causes hematologic toxicity. 8
Common Pitfalls to Avoid
Do not continue tenofovir at any dose in patients with CrCl ≤30 mL/min when alternatives like zidovudine or abacavir are available—the nephrotoxicity risk outweighs any perceived benefit. 7
Do not use standard-dose lamivudine (300 mg daily) at CrCl 30 mL/min—this constitutes overdosing and increases toxicity risk. 1, 5
Do not misinterpret the creatinine increase from dolutegravir as worsening renal function—this is a benign pharmacologic effect on creatinine secretion, not true nephrotoxicity. 5, 6
Monitor for zidovudine-related hematologic toxicity (anemia, neutropenia) with regular complete blood counts, as this is the primary concern with AZT, particularly in patients with advanced disease or low baseline counts. 1