부산대학교 도서관

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-naïve 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 ≥60 ml/min and a serum phosphorus ≥2.2 mg/dl. RESULTS: The incidences of grades 1 (≥0.5 mg/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 1 (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 (Δ) of mean serum phosphorus levels from baseline in both groups was similar (Δ 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 Fanconiʼs 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.