Tenofovir Alafenamide Fumarate-Associated Fanconi Syndrome

Introduction: Tenofovir is a nucleotide analogue used in the treatment of HIV. Tenofovir disoproxil fumarate (TDF) is known to cause decreased bone mineral density and tubulopathy, including Fanconi syndrome. Fanconi syndrome is characterized by urinary loss of phosphate, glucose, uric acid, amino acids, and bicarbonate due to proximal tubule dysfunction. A newer pro-drug formulation, Tenofovir alafenamide (TAF) allows higher intracellular drug concentrations, permitting lower dosing and decreased side effects. While TDF associated Fanconi syndrome is commonly reported in literature, there are only rare reports of TAF associated Fanconi syndrome. We present a case of an exacerbation of Fanconi syndrome after exposure to TAF. Case Description: A 76-year-old male with HIV and CKD presented to the emergency department with right foot pain and swelling. He also reported fatigue, increased thirst, weight loss, and urinary frequency. His vital signs were normal, and his labs were remarkable for hypokalemia of 2.3 mmol/L, phosphorus 2 mg/dL, bicarbonate 20 mmol/L, creatinine 1.87 mg/dL, and eGFR 37 mL/min/1.73 m2. His foot x-ray revealed a Lisfranc fracture. Despite aggressive supplementation and improvement in his creatinine, the patient continued to have hypophosphatemia and hypokalemia which raised concern for renal tubular dysfunction. Further studies revealed fractional excretion of uric acid of 21.9%, fractional excretion of potassium of 62.4%, aminoaciduria, glucosuria, and proteinuria. A diagnosis of Fanconi syndrome was made. Discussion: Notably, the patient had previously been on TDF which was discontinued years prior due to renal toxicity. The patient had been stable on darunavir, ritonavir, and raltegravir, but this was changed to a combined bictegravir-emtricitabine-tenofovir alafenamide for simplicity just prior to his presentation. His pathologic fracture suggested an underlying chronic proximal tubulopathy from his previous TDF use, also evidenced by persistent low-level proteinuria, glucosuria, and mild hypokalemia for several years. His development of acute and severe electrolyte disturbances after initiation of TAF is concerning for acute worsening of preexisting Fanconi syndrome. This case highlights that while TAF is generally considered safer, there is still risk of renal toxicity, particularly when renal tubular dysfunction is already present.