Should Truvada (emtricitabine/tenofovir disoproxil fumarate) be discontinued in patients with impaired renal function, specifically those with a glomerular filtration rate (gFR) below 60?

Should Truvada Be Discontinued When eGFR Falls Below 60 mL/min/1.73m²?

For HIV treatment, Truvada should not be automatically discontinued when eGFR drops below 60 mL/min/1.73m², but rather dose-adjusted and closely monitored; however, for HIV PrEP, Truvada is not recommended when eGFR falls below 60 mL/min/1.73m² and should be discontinued. 1

Context-Specific Recommendations

For HIV Treatment (Therapeutic Use)

Dose adjustment rather than discontinuation is the appropriate strategy for eGFR 30-59 mL/min/1.73m²:

• Continue Truvada with dosing interval adjustment for patients with eGFR 30-49 mL/min/1.73m² while implementing close monitoring of renal function 1
• The FDA label explicitly states that Truvada is not recommended only when eGFR falls below 30 mL/min/1.73m² or in patients requiring hemodialysis 1
• Discontinue immediately if eGFR decreases by >25% from baseline AND drops below 50 mL/min/1.73m², particularly with evidence of proximal tubular dysfunction or worsening proteinuria 2

For HIV PrEP (Prevention)

Discontinue Truvada for PrEP when eGFR drops below 60 mL/min/1.73m²:

• Truvada for HIV-1 PrEP is not recommended in uninfected individuals with eGFR less than 60 mL/min/1.73m² 1
• If eGFR decline is observed during PrEP use, re-assess potential risks and benefits of continued use 1

Monitoring Algorithm

Implement this structured monitoring approach for all patients on Truvada:

• Baseline assessment: Measure serum creatinine, eGFR, urine glucose, and urine protein before initiating Truvada 1
• Ongoing monitoring: Check renal function every 3-6 months for patients with eGFR 30-60 mL/min/1.73m² 2
• High-risk patients: Monitor twice yearly if receiving Truvada plus ritonavir or cobicistat 3
• In chronic kidney disease: Also assess serum phosphorus levels 1

Critical Decision Points for Discontinuation

Discontinue Truvada immediately under these specific circumstances:

• Development of Fanconi syndrome (proximal renal tubular injury with severe hypophosphatemia, normoglycemic glycosuria, proteinuria, metabolic acidosis) 3, 1
• Acute kidney injury with suspected tenofovir toxicity 4
• eGFR persistently below 30 mL/min/1.73m² for HIV treatment 1
• Rapid decline in kidney function (>25% decrease from baseline with eGFR dropping to <50 mL/min/1.73m²) 2, 4
• New onset or worsening proteinuria/albuminuria that doesn't improve after addressing reversible causes 4

Alternative Antiretroviral Options

When discontinuation is necessary, consider these alternatives:

• Tenofovir alafenamide (TAF): Preferred alternative with significantly less renal toxicity 3
• Abacavir: The only nucleoside analogue requiring no dose adjustment for renal insufficiency (requires HLA-B*57:01 screening first) 2
• Dose-adjusted TDF: Useful if concomitant hepatitis B requires treatment and eGFR is 30-49 mL/min/1.73m² 4

Risk Factors Requiring Enhanced Vigilance

These factors increase tenofovir nephrotoxicity risk and warrant more aggressive monitoring:

• Concurrent use of ritonavir-boosted protease inhibitors or cobicistat 3, 1
• Baseline renal insufficiency 4
• Concurrent nephrotoxic medications (NSAIDs, aminoglycosides) 1
• Comorbid hypertension, diabetes, or hepatitis C co-infection 2, 5
• Age ≥50 years 5
• CD4+ count <350 cells/mm³ 5

Common Pitfalls to Avoid

Avoid these critical errors in managing Truvada-related renal dysfunction:

• Don't assume other causes aren't present: Actively exclude HIV-associated nephropathy, hypertensive nephrosclerosis, diabetic nephropathy, and other nephrotoxic drugs before attributing renal decline solely to tenofovir 4
• Don't rely solely on eGFR: Monitor for signs of tubular dysfunction including glycosuria, phosphaturia (fractional excretion of phosphate >20%), and proteinuria, as tubular damage can occur even with preserved eGFR 6
• Don't ignore bone manifestations: Persistent bone pain, pain in extremities, fractures, or muscular weakness may indicate proximal renal tubulopathy requiring immediate evaluation 1
• Don't continue nephrotoxic co-medications: Avoid concurrent NSAIDs, particularly high-dose or multiple agents, as acute renal failure has been reported even in stable patients 1
• Don't expect complete recovery: Even after TDF discontinuation, most patients show improvement but do not return to baseline eGFR, indicating permanent renal function decline 6

Evidence Strength Considerations

The FDA drug label provides the highest quality guidance for this decision 1. The distinction between therapeutic use (dose adjustment at eGFR <60) versus PrEP use (discontinuation at eGFR <60) is clearly delineated in regulatory guidance. Research evidence confirms that tenofovir-induced tubular dysfunction can develop after years of therapy even in those with normal baseline kidney function 6, and that past tenofovir exposure is independently associated with decreased GFR 5.