Renal function with use of a tenofovir-containing initial antiretroviral regimen

Objectives:To determine whether tenofovir disoproxil fumarate (TDF) is associated with renal dysfunction when used as part of an initial antiretroviral regimen and to assess the effect of ritonavir-boosted protease inhibitor (PI/r) coadministration on renal function in TDF-treated patients. Design:Analysis from a prospective observational cohort. Methods:We compared all antiretroviral-naive patients with an estimated glomerular filtration rate (eGFR) of more than 50 ml/min per 1.73 m2 (modification of diet in renal disease equation) who initiated either TDF (n = 201) or any alternative nucleoside reverse transcriptase inhibitor (NRTI) (n = 231) after 1 January 2002. Results:Patients taking both TDF and NRTIs experienced an initial decline in eGFR during the first 180 days of therapy, but eGFR stabilized between 180 and 720 days. There was no difference between TDF and NRTI use in 25 or 50% decline in eGFR at 1 or 2 years or in change in eGFR at 6, 12, or 24 months. Those taking TDF and a PI/r had a greater median decline in eGFR than those taking TDF and a non-NRTI at 6 months (P = 0.01), with trends at 12 (P = 0.08) and 24 months (P = 0.08). There was no difference in median GFR decline between those on an NRTI and PI/r vs. an NRTI and non-NRTI. Conclusion:Our data are consistent with results of clinical trials, which have shown no evidence of renal toxicity when TDF is used as part of an initial regimen. Our results support the use of TDF as a component of the initial antiretroviral regimen, and suggest that the eGFR should be monitored more closely when TDF is used with a PI/r.

[1]  G. Rhodes,et al.  Lack of Evidence for an Effect of Lopinavir/Ritonavir on Tenofovir Renal Clearance , 2008, Clinical pharmacology and therapeutics.

[2]  J. Chmiel,et al.  Renal function in patients receiving tenofovir with ritonavir/lopinavir or ritonavir/atazanavir in the HIV Outpatient Study (HOPS) cohort. , 2006, Journal of acquired immune deficiency syndromes.

[3]  M. Johnson,et al.  A lopinavir/ritonavir-based once-daily regimen results in better compliance and is non-inferior to a twice-daily regimen through 96 weeks. , 2007, AIDS research and human retroviruses.

[4]  J. Rossert,et al.  Fanconi syndrome and renal failure induced by tenofovir: a first case report. , 2002, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[5]  K. Weissenborn,et al.  Neurological and neuropsychiatric syndromes associated with liver disease. , 2005, AIDS.

[6]  A. Winston,et al.  Minor changes in calculated creatinine clearance and anion‐gap are associated with tenofovir disoproxil fumarate‐containing highly active antiretroviral therapy , 2006, HIV medicine.

[7]  Richard D Moore,et al.  Changes in renal function associated with tenofovir disoproxil fumarate treatment, compared with nucleoside reverse-transcriptase inhibitor treatment. , 2005, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[8]  P. Abraham,et al.  Acute renal failure and Fanconi syndrome in an AIDS patient on tenofovir treatment--case report and review of literature. , 2005, The Journal of infection.

[9]  Joel E Gallant,et al.  Tenofovir DF, emtricitabine, and efavirenz vs. zidovudine, lamivudine, and efavirenz for HIV. , 2006, The New England journal of medicine.

[10]  R. Haubrich,et al.  Greater tenofovir-associated renal function decline with protease inhibitor-based versus nonnucleoside reverse-transcriptase inhibitor-based therapy. , 2008, The Journal of infectious diseases.

[11]  H. Izzedine,et al.  Renal tubular transporters and antiviral drugs: an update , 2005, AIDS.

[12]  Tom Greene,et al.  Using Standardized Serum Creatinine Values in the Modification of Diet in Renal Disease Study Equation for Estimating Glomerular Filtration Rate , 2006, Annals of Internal Medicine.

[13]  J. Gallant,et al.  Long-term renal safety of tenofovir disoproxil fumarate in antiretroviral-naive HIV-1-infected patients. Data from a double-blind randomized active-controlled multicentre study. , 2005, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[14]  J. Hulot,et al.  Renal safety of tenofovir in HIV treatment-experienced patients , 2004, AIDS.

[15]  R. Moore,et al.  Understanding the clinical and economic outcomes of HIV therapy: the Johns Hopkins HIV clinical practice cohort. , 1998, Journal of acquired immune deficiency syndromes and human retrovirology : official publication of the International Retrovirology Association.

[16]  J. van Lunzen,et al.  Efficacy and safety of once-daily darunavir/ritonavir versus lopinavir/ritonavir in treatment-naive HIV-1-infected patients at week 48 , 2008, AIDS.

[17]  S. Mauss,et al.  Antiretroviral therapy with tenofovir is associated with mild renal dysfunction , 2005, AIDS.

[18]  K. Robinson,et al.  Mechanism of Active Renal Tubular Efflux of Tenofovir , 2006, Antimicrobial Agents and Chemotherapy.

[19]  Yuichi Sugiyama,et al.  Functional Involvement of Multidrug Resistance-Associated Protein 4 (MRP4/ABCC4) in the Renal Elimination of the Antiviral Drugs Adefovir and Tenofovir , 2007, Molecular Pharmacology.

[20]  R. Ebrahimi,et al.  Pharmacokinetics and Safety of Tenofovir Disoproxil Fumarate on Coadministration With Lopinavir/Ritonavir , 2006, Journal of acquired immune deficiency syndromes.

[21]  Joel E Gallant,et al.  Efficacy and safety of tenofovir DF vs stavudine in combination therapy in antiretroviral-naive patients: a 3-year randomized trial. , 2004, JAMA.

[22]  Samir K. Gupta Tenofovir and changes in renal function. , 2005, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[23]  Hassane Izzedine,et al.  Antiviral drug-induced nephrotoxicity. , 2005, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[24]  I. Hidalgo,et al.  Effects of Human Immunodeficiency Virus Protease Inhibitors on the Intestinal Absorption of Tenofovir Disoproxil Fumarate In Vitro , 2007, Antimicrobial Agents and Chemotherapy.

[25]  Richard D Moore,et al.  Reply to Gupta , 2005 .

[26]  S. Urien,et al.  Population Pharmacokinetics of Tenofovir in Human Immunodeficiency Virus-Infected Patients Taking Highly Active Antiretroviral Therapy , 2008, Antimicrobial Agents and Chemotherapy.

[27]  D. Podzamczer,et al.  A Once-Daily Lopinavir/Ritonavir-Based Regimen Is Noninferior to Twice-Daily Dosing and Results in Similar Safety and Tolerability in Antiretroviral-Naive Subjects Through 48 Weeks , 2009, Journal of acquired immune deficiency syndromes.

[28]  C. Aquilante,et al.  The Effect of Lopinavir/Ritonavir on the Renal Clearance of Tenofovir in HIV‐infected Patients , 2008, Clinical pharmacology and therapeutics.

[29]  G. Braden,et al.  Tenofovir-associated acute and chronic kidney disease: a case of multiple drug interactions. , 2006, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.