Never Too Late: A Case Report of Severe Fanconi Syndrome Developing After More than a Decade of Silent Tenofovir Disoproxil Fumarate Exposure

Background and Clinical Significance: Tenofovir disoproxil fumarate (TDF) is a widely prescribed nucleotide reverse transcriptase inhibitor (NtRTI) for HIV-1 infection. Though generally well-tolerated, proximal renal tubulopathy resulting in full-blown Fanconi syndrome remains a rare but severe complication (<0.1%). Case Presentation: We present the case of a 52-year-old female living with HIV-1 (diagnosed in 1999, CDC stage A3) who had been treated with a TDF-based antiretroviral regimen for 12 years. Upon admission, she complained of progressive bone pain and polyuria over the preceding six months. Laboratory investigations revealed profound hypokalemia, severe hypophosphatemia, hypouricemia, elevated alkaline phosphatase (ALP) and a decline in renal function (creatinine 1.3 mg/dL from a baseline of 0.7 mg/dL). Arterial blood gas (ABG) analysis showed a normal anion gap hyperchloremic metabolic acidosis alongside respiratory acidosis. Urinalysis demonstrated profound glycosuria in the setting of normal blood glucose levels, coupled with increased 24 h urinary excretion of potassium and phosphorus. A bone scintigraphy demonstrated a “super scan” pattern of metabolic etiology, establishing secondary osteomalacia driven by renal phosphate wasting. Secondary hyperparathyroidism and severe vitamin D3 deficiency were also recorded. The diagnosis of TDF-induced Fanconi syndrome was established. TDF was discontinued, and her antiretroviral regimen was modified to tenofovir alafenamide fumarate (TAF), emtricitabine (FTC), darunavir, and ritonavir, combined with vitamin D supplementation. Over a 6-month follow-up period, renal function normalized, electrolyte wasting resolved, and metabolic acidosis completely reversed. Conclusions: This case highlights that TDF-induced proximal tubulopathy can manifest even after a decade of uneventful therapy, particularly when co-administered with a boosted protease inhibitor.