Background: Tenofovir (TDF) is close to adefovir and cidofovir, 2 other nucleotide analogues that have been previously involved in renal tubular dysfunction. In short-term clinical trials, TDF did not exhibit more frequent nephrotoxicity compared to placebo. We observed 3 cases of HIV-infected patients (pts) who presented Fanconi syndrome while taking an antiretroviral regimen containing TDF.

Methods: Case study in a single HIV outpatient clinics.

Results: Eighty-one (81) antiretroviral-experienced pts started a TDF-containing antiretroviral regimen between March 2001 and March 2002, among whom 74 had more than 6 months of cumulative TDF exposition as of October 2002. Among these 74 pts, 3 (2 women and 1 man) developed renal tubular injury, with hypophosphoremia (0.39; 0.47; 0.41 mM/l for pt 1, 2, and 3, respectively), glycosuria (105; 7.7; and 0.8 g/l for pt 1, 2, and 3, respectively), proteinuria (1.22; 1.6; 1.15 g/l for pt 1, 2, and 3, respectively), and a decrease in creatinine clearance (of 32, 47, and 20% for pt 1, 2, and 3, respectively). The first biological signs of tubular injury appeared after a duration of TDF therapy of 8, 11, and 9 months for pt 1, 2, and 3, respectively, and resolved within less than 3 months after TDF was stopped. Two pts (n°1 and 2) had myalgias and/or paresthesias possibly related to hypophosphoremia which resolved within 1 wk after interruption of TDF. All pts had a low weight (< 60 kgs), none had diabetes or hyperlactatemia. All pts received low doses of ritonavir and 1 pt received didanosine (patient n°3). However, in 2 pts (n°1 and n°3), only TDF was stopped and the signs resolved.

Conclusions: Long-term TDF therapy may be associated with Fanconi syndrome which is related to injury of proximal tubular cells in the nephron and may lead to renal failure. Given the reversibility of this disorder, we recommend periodic screening for the pts on long-term TDF therapy, by measuring phosphoremia, glycosuria, proteinuria, and renal function.