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 > or =60 ml/min and a serum phosphorus > or =2.2 mg/dl. RESULTS: The incidences of grades 1 (> or =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 (Delta) 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.
RCT Entities:
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-infectedpatients. 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 > or =60 ml/min and a serum phosphorus > or =2.2 mg/dl. RESULTS: The incidences of grades 1 (> or =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 (Delta) 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-infectedpatients with normal renal function at baseline.
Authors: Francesc Vidal; Joan Carles Domingo; Jordi Guallar; Maria Saumoy; Begoña Cordobilla; Rainel Sánchez de la Rosa; Marta Giralt; Maria Luisa Alvarez; Miguel López-Dupla; Ferran Torres; Francesc Villarroya; Tomas Cihlar; Pere Domingo Journal: Antimicrob Agents Chemother Date: 2006-08-28 Impact factor: 5.191
Authors: Carl Grunfeld; Donald P Kotler; Donna K Arnett; Julian M Falutz; Steven M Haffner; Paul Hruz; Henry Masur; James B Meigs; Kathleen Mulligan; Peter Reiss; Katherine Samaras Journal: Circulation Date: 2008-06-19 Impact factor: 29.690
Authors: Lene Ryom; Amanda Mocroft; Ole Kirk; Signe W Worm; David A Kamara; Peter Reiss; Michael Ross; Christoph A Fux; Philippe Morlat; Olivier Moranne; Colette Smith; Jens D Lundgren Journal: J Infect Dis Date: 2013-02-04 Impact factor: 5.226
Authors: Benjamin H Chi; Albert Mwango; Mark Giganti; Lloyd B Mulenga; Bushimbwa Tambatamba-Chapula; Stewart E Reid; Carolyn Bolton-Moore; Namwinga Chintu; Priscilla L Mulenga; Elizabeth M Stringer; Robert Sheneberger; Peter Mwaba; Jeffrey S A Stringer Journal: J Acquir Immune Defic Syndr Date: 2010-05-01 Impact factor: 3.731
Authors: Murli Purswani; Kunjal Patel; Jeffrey B Kopp; George R Seage; Miriam C Chernoff; Rohan Hazra; George K Siberry; Lynne M Mofenson; Gwendolyn B Scott; Russell B Van Dyke Journal: Pediatr Infect Dis J Date: 2013-05 Impact factor: 2.129
Authors: Colleen Hadigan; Elizabeth Edwards; Alice Rosenberg; Julia B Purdy; Estee Fleischman; Lilian Howard; JoAnn M Mican; Karmini Sampath; Akinbowale Oyalowo; Antoinette Johnson; Alexandra Adler; Catherine Rehm; Margo Smith; Leon Lai; Jeffrey B Kopp Journal: Am J Nephrol Date: 2013-04-20 Impact factor: 3.754