Renal and Bone Toxicity with the Use of Tenofovir: Understanding at the End.

The use of tenofovir disoproxil fumarate has been associated with side effects on renal function and bone mineral density, but whether this toxicity is of clinical relevance in the middle or long term is highly debated. Current knowledge supports that the use of and time on tenofovir disoproxil fumarate, modulated by other factors such as age, baseline renal function, or classical risk factors, could led to progressive wasting in the urine of low molecular weight proteins, phosphate, uric acid, or glucose. This "partial" Fanconi syndrome seems to be slowly progressive, with increases in the proportion of patients and in the severity of different tubular abnormalities with the long term use of tenofovir disoproxil fumarate. Although progression to chronic kidney disease is relatively rare in patients on tenofovir disoproxil fumarate, in part attributed to the capacity of kidneys to compensate for loss of functioning nephrons, the severity of tubular dysfunction is associated with greater kidney function decline. In large cohorts, the use of tenofovir disoproxil fumarate is one of the main risk factors associated to chronic kidney disease. In addition, hyperphosphaturia secondary to tubular dysfunction could alter the interplay between bone, kidney, and regulatory hormones, leading to progressive bone loss in a similar manner, but in a lesser extent, to hypophosphatemic osteomalacia observed in the Fanconi syndrome. This component of osteomalacia secondary to altered phosphate metabolism explains the partial improvement observed with vitamin D supplementation, the association with altered bone-specific alkaline phosphatase, and the rapid benefit in terms of bone mineral density after tenofovir disoproxil fumarate discontinuation.

Effect of a monthly dose of calcidiol in improving vitamin D deficiency and secondary hyperparathyroidism in HIV-infected patients.

There are no data about the optimal supplementation therapy in HIV-infected patients with vitamin D (25OHD) deficiency. The aim of this study was to assess the effect of an oral monthly dose of 16,000 IU calcidiol. We performed a longitudinal cohort study of 365 HIV-infected patients (24 % females) was with sequential determinations of 25OHD, serum parathyroid hormone (PTH), calcium, and alkaline phosphatase. The efficacy and safety of supplementation in 123 patients were compared against dietary and sun exposure advice. Overall, mean baseline 25OHD levels were 19.1 ng/ml (IQR 12-23.6), 63 % of patients had 25OHD deficiency and 27 % secondary hyperparathyroidism. After a median time of 9.3 months (95.61 patients-year on-treatment), 25OHD levels increased in comparison with non-supplemented patients (+16.4 vs. +3.2 ng/ml; p < 0.01), decreasing the rate of 25OHD deficiency (from 84 to 24 %), and decreasing serum PTH (-4.9 pg/ml) and the rate of secondary hyperparathyroidism (from 43 to 31 %; p < 0.001). This improvement was observed irrespective of HIV/HCV coinfection or the use of efavirenz. In a regression analysis, adjusting by seasonality, a lower baseline 25OHD was associated with persistence of deficiency (relative risk, RR 1.07; 95 % CI 1.03-1.1; p < 0.001), whereas calcidiol supplementation was the only factor associated with significant improvement (RR 0.38; 95 % CI 0.12-0.46; p < 0.001). This monthly dose showed no clinical toxicity, and no patient had 25OHD levels above 100 ng/ml, nor hypercalcemia. The use of monthly calcidiol is safe, easy to take, and largely effective to improve vitamin D deficiency and secondary hyperparathyroidism in HIV-infected patients.