NDT Advance Access originally published online on March 1, 2005
Nephrology Dialysis Transplantation 2005 20(4):743-746; doi:10.1093/ndt/gfh658
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Long-term renal safety of tenofovir disoproxil fumarate in antiretroviral-naïve HIV-1-infected patients. Data from a double-blind randomized active-controlled multicentre study
Departments of 1 Nephrology and 2 Clinical Pharmacology, Pitie-Salpêtrière Hospital, 3 Department of Infectious Diseases, Kremlin Bicêtre Hospital, Paris, France, 4 Johns Hopkins University School of Medicine, Baltimore, MD, 5 University Hospital, J. W. Goethe-Universität, Frankfurt, Germany and 6 Gilead Sciences, Foster City, CA, USA
Correspondence and offprint requests to: Hassane Izzedine, MD, Department of Nephrology, Pitié Salpêtrière Hospital, 47–83 Boulevard de l'Hôpital, 75013 Paris, France. Email: hassan.izzedine{at}psl.ap-hop-paris.fr
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 (
) of mean serum phosphorus levels from baseline in both groups was similar ( 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.
Keywords: long-term renal safety; tenofovir; tubulopathy
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  K. K. A. Van Rompay, L. Durand-Gasselin, L. L. Brignolo, A. S. Ray, K. Abel, T. Cihlar, A. Spinner, C. Jerome, J. Moore, B. P. Kearney, et al. Chronic Administration of Tenofovir to Rhesus Macaques from Infancy through Adulthood and Pregnancy: Summary of Pharmacokinetics and Biological and Virological Effects Antimicrob. Agents Chemother., September 1, 2008; 52(9): 3144 - 3160. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Grunfeld, D. P. Kotler, D. K. Arnett, J. M. Falutz, S. M. Haffner, P. Hruz, H. Masur, J. B. Meigs, K. Mulligan, P. Reiss, et al. Contribution of Metabolic and Anthropometric Abnormalities to Cardiovascular Disease Risk Factors Circulation, July 8, 2008; 118(2): e20 - e28. [Full Text] [PDF]
|
|
|
|
 |
|
 H. Izzedine, A. Baumelou, and G. Deray Acute renal failure in HIV patients Nephrol. Dial. Transplant., October 1, 2007; 22(10): 2757 - 2762. [Full Text] [PDF]
|
|
|
|
 |
|
 B. Young, K. Buchacz, R. K. Baker, A. C. Moorman, K. C. Wood, J. Chmiel, J. T. Brooks, and HIV Outpatient Study Investigators Renal Function in Tenofovir-Exposed and Tenofovir-Unexposed Patients Receiving Highly Active Antiretroviral Therapy in the HIV Outpatient Study J Int Assoc Physicians AIDS Care (Chic Ill), September 1, 2007; 6(3): 178 - 187. [Abstract] [PDF]
|
|
|
|
 |
|
 T. I. de Silva, F. A. Post, M. D. Griffin, and D. H. Dockrell HIV-1 Infection and the Kidney: An Evolving Challenge in HIV Medicine Mayo Clin. Proc., September 1, 2007; 82(9): 1103 - 1116. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Gayet-Ageron, J. Ananworanich, T. Jupimai, P. Chetchotisakd, W. Prasithsirikul, S. Ubolyam, M. Le Braz, K. Ruxrungtham, J. F. Rooney, B. Hirschel, et al. No change in calculated creatinine clearance after tenofovir initiation among Thai patients J. Antimicrob. Chemother., May 1, 2007; 59(5): 1034 - 1037. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Vidal, J. C. Domingo, J. Guallar, M. Saumoy, B. Cordobilla, R. Sanchez de la Rosa, M. Giralt, M. L. Alvarez, M. Lopez-Dupla, F. Torres, et al. In Vitro Cytotoxicity and Mitochondrial Toxicity of Tenofovir Alone and in Combination with Other Antiretrovirals in Human Renal Proximal Tubule Cells Antimicrob. Agents Chemother., November 1, 2006; 50(11): 3824 - 3832. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. E. Delaney IV, A. S. Ray, H. Yang, X. Qi, S. Xiong, Y. Zhu, and M. D. Miller Intracellular Metabolism and In Vitro Activity of Tenofovir against Hepatitis B Virus. Antimicrob. Agents Chemother., July 1, 2006; 50(7): 2471 - 2477. [Abstract] [Full Text] [PDF]
|
|