OBJECTIVE

To determine the evolution of renal function in highly treatment-experienced patients with normal renal function at baseline receiving tenofovir disoproxil fumarate (TDF) as part of a fixed combined antiretroviral regimen and to identify prognostic factors of change in renal function, including tenofovir concentrations.

METHODS

A prospective 48-week open-label trial was carried out, evaluating the safety of TDF, associated with atazanavir/ritonavir, and optimized nucleoside reverse transcriptase inhibitors, in patients with documented failure in previous treatments. Statistical analysis was performed on an intent-to-treat basis.

RESULTS

Fifty-three patients were included, with a median CD4+ T-cell count of 206 x 10(6)/l and a median HIV RNA level of 5 log10 copies/ml. All patients had normal serum creatinine levels and creatinine clearances (CL(Cr)) at baseline, which were stable within the 2 months preceding inclusion. Two patients discontinued TDF as a result of severe renal impairment. Two patients never started TDF. A total of 49 patients without clinical nephrotoxicity were analysed. The median creatinine level increased significantly from baseline to week 48 (+0.04 mg/dl [+5.8%]; P = 0.008), and the median CL(Cr) decreased significantly (-7.8 ml/min [-7.6%]; P = 0.005). Trough tenofovir concentration was not associated with change in CL(Cr), (P = 0.79). No risk factors, including tenofovir plasma trough levels, were significantly associated with change in CL(Cr) at week 24.

CONCLUSIONS

This study confirms that TDF-related severe nephrotoxicity is an uncommon event. In patients without clinical nephrotoxicity, the use of TDF during a 1-year period was associated with a slight but significant alteration of renal function, which was not associated with increased trough concentration.