Can Truvada (tenofovir disoproxil fumarate and emtricitabine) cause hyponatremia?

Truvada and Hyponatremia: Clinical Considerations

Truvada (tenofovir disoproxil fumarate and emtricitabine) has not been established as a cause of hyponatremia in available medical literature and guidelines.

Mechanism and Risk Assessment

Truvada, a combination of tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC), is primarily associated with other adverse effects rather than hyponatremia:

• TDF is most commonly associated with renal toxicity, specifically proximal tubular dysfunction and decreased glomerular filtration rate 1
• The primary renal concerns with TDF include:
  • Acute kidney injury
  • Chronic kidney disease
  • Fanconi syndrome (proximal tubular dysfunction)
  • Small but definite negative impact on kidney function (up to 10% decrease in GFR) 1

Evidence Against Hyponatremia Association

Several high-quality studies and guidelines do not list hyponatremia as a known adverse effect of Truvada:

• In the DISCOVER trial, which compared TDF/FTC with tenofovir alafenamide (TAF)/FTC for HIV pre-exposure prophylaxis, hyponatremia was not reported as an adverse event 2
• A systematic review of renal and bone safety of efavirenz+FTC+TDF did not identify hyponatremia as a reported adverse effect 3
• The Partners PrEP Study specifically evaluated tubular dysfunction with FTC-TDF and did not report hyponatremia as a concern 4

Known Adverse Effects of Truvada

Instead of hyponatremia, clinicians should monitor for the following established adverse effects:

1. Renal effects:

   • Decreased GFR
   • Proximal tubular dysfunction
   • Increased serum creatinine 1

2. Bone effects:

   • Reduced bone mineral density
   • Increased bone turnover markers 3

3. Metabolic effects:

   • Lactic acidosis (rare but serious)
   • Hepatic steatosis 5

Monitoring Recommendations

For patients on Truvada, guidelines recommend:

• Baseline renal function assessment using creatinine-based eGFR
• Follow-up assessment at 1-3 months after initiation
• Regular monitoring every 6-12 months if stable 1
• More frequent monitoring for patients with:
  • Established CKD (eGFR <50 mL/min/1.73 m²)
  • Hypertension
  • Diabetes
  • HIV-associated kidney disease
  • Hepatitis B or C co-infection
  • Concomitant use with ritonavir-boosted protease inhibitors 1

Clinical Implications

If a patient on Truvada develops hyponatremia:

• Consider alternative causes of hyponatremia, as Truvada is not a known cause
• Evaluate for other medications that commonly cause hyponatremia (e.g., certain anticonvulsants like carbamazepine and oxcarbazepine) 6
• Assess for other conditions that may cause hyponatremia (SIADH, heart failure, cirrhosis, hypothyroidism)
• Do not discontinue Truvada solely based on hyponatremia unless other causes have been ruled out

Alternative Options

For patients with renal concerns who require HIV pre-exposure prophylaxis:

• Tenofovir alafenamide (TAF)/emtricitabine shows improved renal safety compared to TDF/emtricitabine 2
• TAF/FTC is recommended as an alternative for those with or at risk for kidney dysfunction, osteopenia, or osteoporosis 7

Conclusion

Based on current evidence, Truvada (TDF/FTC) has not been established as a cause of hyponatremia. Clinicians should focus on monitoring for known adverse effects, particularly renal dysfunction and bone mineral density changes, while considering other causes if hyponatremia develops in a patient taking Truvada.