Long-term renal safety of tenofovir disoproxil fumurate in antiretroviral-naive HIV-1-infected patients. Data from a double-blind randomized active-controlled multicentre study

Background. Tenofovir disoproxil fumarate (TDF) was developed for the treatment of human immunodeficiency virus (HIV) infection. However, controlled data are sparse on the long-term renal tolerability of TDF at the currently approved daily dose of 300 mg in treatment-naive HIV-infected patients. Methods. Over 144 weeks, this 600 patient, multicentre randomized, placebo-controlled, double-blind trial compared stavudine (301 patients) and TDF (299 patients), both administered in combination with lamivudine and efavirenz, in antiretroviral-naive patients. TDF or placebo and stavudine or placebo were administered in an open-label fashion. All medications were taken orally. At screening, all patients had serum creatinines < 1.5 mg/dl, calculated creatinine clearances >= 60ml/min and a serum phosphorus >= 2.2mg/dl. Results. The incidences of grades 1 (>= 0.5mg/dl increase from baseline), 2 (2.1-3.0 mg/dl) and 3 (3.1-6.0 mg/dl) serum creatinine elevations at week 144 were 4, < 1 and 0%, respectively, in the TDF group and 2, 0 and < 1% in the stavudine control group (P = NS). There were no grade 4 (> 6 mg/dl) serum creatinine elevations. At week 144, there was no change from baseline in the mean (0.83 mg/dl) serum creatinine in the TDF group compared with a 0.1 mg/dl decrease from baseline (0.83 mg/dl) in the stavudine control group. The incidences of grades I (2.0-2.2 mg/dl), 2 (1.5-1.9 mg/dl) and 3 (1.0-1.4 mg/dl) hypophosphataemia at week 144 were 4, 3 and < 1%, respectively, in the TDF group and 4, 2 and < 1% in the control group (P=NS). No patient experienced grade 4 (< 1.0 mg/dl) hypophosphataemia. At week 144, the decrease (A) of mean serum phosphorus levels from baseline in both groups was similar (Delta 0.2 from 3.6 mg/dl for the TDF group, and 0.1 from 3.5 mg/dl for the stavudine control group). No patient developed Fanconi's syndrome or proximal renal tubular dysfunction during the study. Conclusion. Through 144 weeks, TDF and stavudine, each administered in combination with efavirenz and lamivudine, had similar renal safety profiles in treatment-naive HIV-infected patients with normal renal function at baseline.