Can Truvada (emtricitabine and tenofovir disoproxil fumarate) cause worsening kidney function or liver function, particularly in patients with pre-existing kidney or liver disease?

Can Truvada Cause Worsening Kidney or Liver Function?

Yes, Truvada (tenofovir disoproxil fumarate/emtricitabine) can cause significant kidney dysfunction, including acute renal failure and Fanconi syndrome, but does not typically cause liver toxicity—in fact, it may improve liver function in patients with hepatitis B coinfection. 1

Kidney Toxicity: The Primary Concern

Mechanism and Clinical Manifestations

Truvada's tenofovir component causes proximal tubular dysfunction that can manifest as:

• Fanconi syndrome with normoglycemic glycosuria 2
• Hypophosphatemia with phosphate wasting 2, 3
• Proteinuria (typically low-level, non-albumin predominant) 3
• Metabolic acidosis from bicarbonate wasting 2
• Progressive decline in estimated glomerular filtration rate (eGFR) 1

The FDA label explicitly warns that renal impairment, including acute renal failure and Fanconi syndrome, has been reported with tenofovir disoproxil fumarate use. 1

Expected Kidney Function Changes

Even in patients without overt toxicity, tenofovir causes measurable renal effects:

• Mean creatinine increase of 0.03 mg/dL (4.6%) within 12 weeks of starting therapy 4
• Up to 10% decrease in GFR is common and expected 5
• 15.7% of patients develop worsening proteinuria by week 12 4
• Mean eGFR decline of 15.73 mL/min/1.73 m² over 48 months compared to 5.96 mL/min/1.73 m² with entecavir 6

High-Risk Populations Requiring Enhanced Monitoring

Avoid tenofovir or use with extreme caution in patients with: 7, 3

• Baseline eGFR <60 mL/min/1.73 m² (requires dose adjustment or alternative agent) 7, 1
• Pre-existing chronic kidney disease at any stage 7
• Concurrent ritonavir-boosted protease inhibitors (significantly increases tenofovir exposure and nephrotoxicity risk) 7, 2, 3
• Concurrent cobicistat use (increases tenofovir levels) 3
• Age ≥40 years (3.79-fold increased risk of new-onset eGFR <70) 4
• Diabetes mellitus 3, 5
• Hypertension 3, 5
• Hepatitis B or C coinfection (2-3 fold increased CKD risk) 3, 5
• Concurrent nephrotoxic medications, especially NSAIDs 1

Mandatory Monitoring Protocol

Before initiating tenofovir: 1, 7

• Serum creatinine with calculated eGFR (CKD-EPI equation preferred) 3
• Urinalysis for protein, glucose, and blood 3
• Serum phosphorus (if baseline CKD present) 1

During therapy: 7, 5

• Repeat testing at 1-3 months, then every 6 months if stable 7, 5
• Every 3-6 months if risk factors present 5
• More frequent monitoring if eGFR <60 mL/min/1.73 m² 5

When to Discontinue Tenofovir Immediately

Stop tenofovir if any of the following occur: 7, 2, 3

• eGFR drops by >25% from baseline AND decreases to <60 mL/min/1.73 m² 7
• Evidence of proximal tubular dysfunction: euglycemic glycosuria, hypophosphatemia with phosphate wasting, or metabolic acidosis 7, 2
• New-onset or worsening proteinuria 7
• Persistent bone pain, extremity pain, fractures, or muscle weakness (may indicate proximal renal tubulopathy) 1

Alternative Antiretroviral Options

When tenofovir must be avoided or discontinued: 7, 2, 3

• Tenofovir alafenamide (TAF) is the preferred alternative (less nephrotoxic, requires creatinine clearance >30 mL/min) 7, 3
• Abacavir (no dose adjustment needed for renal impairment, but screen for HLA-B*57:01 allele first; avoid if baseline HIV RNA >100,000 copies/mL without integrase inhibitor) 7
• Switch ritonavir-boosted protease inhibitors to darunavir if protease inhibitor needed 3

Dose Adjustment for Renal Impairment

If tenofovir must be continued with reduced kidney function: 1

• CrCl 30-49 mL/min: 300 mg every 48 hours
• CrCl 10-29 mL/min: 300 mg every 72-96 hours
• Hemodialysis patients: 300 mg every 7 days (after dialysis session)
• CrCl <10 mL/min (not on dialysis): No data available; avoid use 1

Liver Function: Not a Primary Concern

Tenofovir does not cause clinically significant liver toxicity. 7, 1 In fact:

• Tenofovir is effective treatment for hepatitis B and may improve liver function in coinfected patients 7
• ALT flares (ALT >2× baseline and >10× ULN) occur in only 2.6% of patients, typically within 4-8 weeks, and resolve without intervention 1
• These flares are accompanied by decreases in HBV DNA and represent immune-mediated viral clearance, not drug toxicity 1
• No evidence of hepatic decompensation attributed to tenofovir in clinical trials 1

Critical Warning for Hepatitis B Patients

Severe acute exacerbation of hepatitis B can occur upon discontinuation of tenofovir in HBV-infected patients. 1 Monitor closely with clinical and laboratory follow-up for at least several months after stopping treatment, especially in patients with advanced liver disease or cirrhosis, as post-treatment hepatitis exacerbation may lead to hepatic decompensation and liver failure. 1

Common Pitfalls to Avoid

• Do not use full-dose tenofovir with ritonavir-boosted protease inhibitors in patients with any renal risk factors 7, 3
• Do not continue tenofovir if TAF or abacavir are available for patients with CKD, rapid eGFR decline (>3-5 mL/min/1.73 m²/year), or high CKD risk 3
• Do not rely on serum creatinine alone—calculate eGFR and check urinalysis for glycosuria and proteinuria 3, 1
• Do not assume small creatinine increases are insignificant—a 0.5 mg/dL increase warrants immediate evaluation 1
• Do not prescribe high-dose or multiple NSAIDs to patients on tenofovir, especially those with renal risk factors (cases of acute renal failure requiring hospitalization and dialysis have been reported) 1