Skip Navigation LinksHome > December 1, 2004 - Volume 37 - Issue 4 > Renal Dysfunction With Tenofovir Disoproxil Fumarate-Contain...
JAIDS Journal of Acquired Immune Deficiency Syndromes:
Clinical Science

Renal Dysfunction With Tenofovir Disoproxil Fumarate-Containing Highly Active Antiretroviral Therapy Regimens Is Not Observed More Frequently: A Cohort and Case-Control Study

Jones, Rachael MRCP*; Stebbing, Justin MRCP, PHD†; Nelson, Mark FRCP*; Moyle, Graeme MD*; Bower, Mark FRCP, PHD*; Mandalia, Sundhiya PHD*; Gazzard, Brian FRCP*

Free Access
Article Outline
Collapse Box

Author Information

From the *Department of HIV and Genitourinary Medicine, The Chelsea and Westminster Hospital, London, United Kingdom; and †Department of Immunology, Division of Investigative Science, Faculty of Medicine, Imperial College of Science, Technology and Medicine, The Chelsea and Westminster Hospital, London, United Kingdom.

Received for publication December 30, 2003;

accepted July 2, 2004.

Reprints: Rachael Jones, Department of HIV and Genitourinary Medicine, The Chelsea and Westminster Hospital, 369 Fulham Road, London SW10 9NH, United Kingdom (e-mail: rachaeljones30@hotmail.com).

Collapse Box

Abstract

Background: Tenofovir disoproxil fumarate (tenofovir DF), the first nucleotide analogue reverse transcriptase inhibitor approved for the treatment of HIV infection, has been associated with renal dysfunction in isolated cases. We investigated the overall incidence and risk of renal dysfunction in individuals receiving tenofovir DF and compared this with other antiretrovirals.

Methods: Data from the Chelsea and Westminster cohort were analyzed to reveal HIV-positive individuals with a creatinine value greater than 120 μmol/L at any time, the upper limit of normal used by our reference laboratory. These individuals were classified according to antiretroviral exposure and time exposed. A matched case-control study was performed comparing patients who had received tenofovir DF and subsequently developed a creatinine value greater than 120 μmol/L against controls who had been treated with tenofovir DF and had not experienced a creatinine elevation.

Results: Of 4183 HIV-positive patients, 1175 were identified as having a recorded creatinine value >120 μmol/L. Comparison of antiretroviral-naive patients and patients exposed to tenofovir DF- and non-tenofovir DF-containing regimens revealed a lower rate ratio and probability of developing a creatinine value >120 μmol/L in patients exposed to tenofovir DF (rate ratio vs. no antiretrovirals = 0.22, 95% confidence interval [CI]: 0.07-0.69; P < 0.001) with no significant difference between HAART regimens, corrected for duration of exposure. Of the 1058 individuals who were exposed to tenofovir DF, 84 (8%) patients experienced a creatinine value >120 μmol/L subsequent to exposure. An alternative etiology of renal dysfunction was found in 75 (90%) of these individuals.

Conclusions: Tenofovir DF is not associated with renal dysfunction more frequently than other antiretroviral drugs, and the occurrence of renal dysfunction in this context is usually attributable to other causes.

The selective targeting of the HIV-1 protease and/or reverse transcriptase has led to decreased morbidity and mortality as a result of infection with HIV-1.1,2 Tenofovir disoproxil fumarate [R-9-(2-phosphonyl-methoxypropyl)adenine, tenofovir DF] is the first nucleotide analogue reverse transcriptase inhibitor (NRTI) to be approved for the treatment of HIV infection.3-6 It has been well tolerated in clinical trials to date, without evidence of long-term toxicity in cohort studies, including the mitochondrial toxicity that has been associated with some NRTIs.7,8 Since its approval in October 2001, tenofovir DF has quickly become a widely used component of antiretroviral regimens for treatment-naive and -experienced patients.9-11 Recent data also indicate that it is able to overcome lamivudine resistance in the treatment of hepatitis B virus.12-14

Cidofovir and adefovir dipivoxil, compounds structurally related to tenofovir DF, have been associated with increased risk for acute renal insufficiency possibly because of tubular accumulation and toxic metabolites.15-17 A small number of cases of tubular injury associated with Fanconi-like syndrome (proximal renal tubular acidosis) in patients with normal baseline renal function have also been reported.18,19 Although there are other isolated cases of renal tubular dysfunction and a report of acute renal failure in a patient with stable chronic renal failure during tenofovir DF therapy,20,21 the frequency of these occurrences in HIV-1-infected individuals receiving tenofovir DF relative to other antiretroviral regimens remains unknown.

Although renal insufficiency is well reported in the context of HIV-1 infection and its treatment,16,22 because of the specific case reports of acute renal failure during tenofovir DF therapy, we investigated the prevalence of renal insufficiency in a large cohort of HIV-1-positive individuals. In comparing such individuals with appropriately matched controls, we established that tenofovir DF does not cause renal failure more frequently than other antiretrovirals and that the occurrence of renal failure in this context is a rare event.

Back to Top | Article Outline

METHODS

The Chelsea and Westminster HIV cohort is one of the largest in Europe, and we prospectively collect routine data on the individuals who attend. HIV-positive patients are seen at regular intervals for clinical assessment; trial follow-up; and biochemical, immunologic, and virologic assessments. We have defined highly active antiretroviral therapy (HAART) as therapy consisting of at least 3 antiretroviral drugs in accordance with published guidelines.23 HAART was begun at this institution on January 1, 1996.

Our reference laboratory denotes 120 μmol/L as the value representing the upper limit of normal for creatinine in men and women. Thus, we defined renal dysfunction as a creatinine value greater than 120 μmol/L at any time and then classified patients according to antiretroviral exposure before this level. Patients who received nucleoside analogue only regimens and those with no antiretroviral history were also examined. The data were analyzed using the Genmod procedure in SAS version 8.0 with loge link and Poisson error distributions. If creatinine levels were greater than 120 μmol/L, NRTI exposure before a creatinine level >120 μmol/L was used; otherwise, the antiretroviral agents at the time of censoring were recorded. Time-dependent variables were studied to investigate the probability of developing a creatinine level >120 μmol/L on different antiretroviral regimens that did and did not contain tenofovir DF.

For the matched case-control study, any patient who had received tenofovir DF and had a creatinine value greater than 120 μmol/L since commencing tenofovir DF (and not before) was identified. Each of these patients was matched to a control who had received tenofovir DF but did not have a raised creatinine value since beginning this antiretroviral. The matching criteria used included (1) line of treatment (experienced with other NRTIs vs. not experienced), (2) inpatient episode while on tenofovir DF for any reason, (3) total duration of combination therapy at the time of starting tenofovir DF (±2 months), (4) baseline CD4 count (±50 cells/mm3), and (5) baseline HIV-1 viral load (±10,000 copies/mL). Data were analyzed in SAS using conditional logistic regression with the Proportion Hazard Regression Model (PHREG) procedure by using the discrete logistic model stratified by the aforementioned criteria.

In those patients receiving tenofovir DF who developed a creatinine level greater than 120 μmol/L, we compared changes in their creatinine from pre-tenofovir DF levels to peak levels and latest creatinine values. Creatinine clearance was calculated in these patients using the formula (the Cockroft and Gault equation):

Equation 1
Equation 1
Image Tools

where F = 1.04 (female patients) and F = 1.23 (male patients) and ideal body weight (IBW in kilograms) = Y + (0.906 to each centimeter greater than 152.4 cm), where Y = 45.5 (female patients) and Y = 50 (male patients). We also calculated creatinine clearances according to the Jeliffe and Chatelut equations.

We performed clinical record searches on all these individuals to establish the presence or absence of any other cause or contributors to renal failure, including nephrotoxic drugs and/or serious intercurrent infections and/or physiologic insult culminating in a decline in renal function. Weights were recorded to establish creatinine clearance. The cause of death for any patient receiving tenofovir DF was also investigated.

In a small audit to investigate the presence of proteinuria in our patients, 100 individuals’ urine samples were dipsticked (Dipsticks; Bayer, Newbury, UK) before and during tenofovir DF treatment. The presence or absence of albuminuria as detected by the dipsticks was recorded at time 0 and 8 to 12 weeks after beginning therapy.

Back to Top | Article Outline

RESULTS

Comparison With Other Antiretrovirals

At this institution, 4183 HIV-1-positive individuals have been followed up during the HAART era, and of these, we have identified 1175 (28%) patients who have ever had a creatinine value greater than 120 μmol/L. In comparison with having received no antiretroviral regimen and receiving regimens containing and not containing tenofovir DF, we observed a lower rate ratio of developing a creatinine level greater than 120 μmol/L in those patients who received tenofovir DF corrected for length of time exposed (Fig. 1). The differences in rate ratios between all HAART regimens that patients were exposed to were not statistically significant after adjustment for duration of exposure (Table 1).

Table 1
Table 1
Image Tools
Figure 1
Figure 1
Image Tools

No use of antiretrovirals was a significant risk factor for an increased creatinine level (see Fig. 1). We observed a statistically significant increase in the incidence of HIV-positive individuals having a creatinine value greater than 120 μmol/L in those individuals who had no history of antiretrovirals (rate ratio = 3.32, 95% confidence interval [CI]: 2.75-3.97; P < 0.001). In addition, nucleoside analogue exposure only (rate ratio = 1.87) was more likely to be associated with an increased creatinine level compared with nucleoside analogue and nonnucleoside reverse transcriptase inhibitor (NNRTI) therapy (rate ratio = 1.13) or nucleoside analogue and protease inhibitor (PI) and NNRTI therapy. Those individuals who received a nucleoside analogue- and PI-containing HAART regimen (rate ratio = 1.87) were not significantly less likely to have a creatinine value greater than 120 μmol/L than those who received a nucleoside analogue only because of wide CIs in the former group (95% CI: 1.53-2.31).

Consistent with these data, the probability of developing a raised creatinine level over time was not significantly increased in those individuals who received tenofovir DF-containing regimens (Fig. 2). Figure 2 also demonstrates that the probability of developing a raised creatinine level over time is similar for those patients who did not receive antiretrovirals or received nucleoside analogues only.

Figure 2
Figure 2
Image Tools
Back to Top | Article Outline
Matched Cohort Study

Using data extracted on September 30, 2003, we identified 1058 patients who have never been prescribed tenofovir DF. Of these, 117 patients were observed to have a creatinine level greater than 120 μmol/L (once), and 33 (28%) of these 117 patients were excluded from matching because of a creatinine level greater than 120 μmol/L before receiving tenofovir DF. Table 2 demonstrates that for the 84 patients who were successfully matched 1:1 with controls, there were no statistically significant differences in renal parameters (ie, creatinine or phosphate) measurements.

Table 2
Table 2
Image Tools
Back to Top | Article Outline
Follow-Up of Patients

Of the 84 patients who developed a raised creatinine level subsequent to receiving tenofovir DF, analysis of patient records revealed the presence of other causes of renal impairment in 75 patients (Table 3). This included nephrotoxic drugs in 13 (15%), serious intercurrent illnesses in 21 (25%), and both in 10 (12%). The baseline characteristics of these individuals, including demographic, ethnic, immunologic, and virologic data, were not significantly different from those of the remainder of the cohort. In 9 individuals exposed to tenofovir DF, creatinine values increased to greater than 120 μmol/L without definite obvious other causes. Three of these individuals had recently received short courses (5 days) of high-dose co-trimoxazole for presumptive Pneumocystis carinii pneumonia (PCP).

Table 3
Table 3
Image Tools

The median creatinine and creatinine clearances before tenofovir DF, at the peak during tenofovir DF, and at the latest values are shown in Figure 3. The rise in creatinine observed in these individuals had partially normalized by the time of the most recent sample. Similarly, the 33 patients who began tenofovir DF with a creatinine value greater than 120 μmol/L showed no significant increases or decreases. There were no correlations observed between CD4 cell count and creatinine or phosphate values at start, peak, or the latest creatinine or phosphate value (Pearson correlation coefficient, r < 0.02 in all cases). A retrospective analysis of phosphate values 3 months before the peak creatinine value demonstrated insignificant positive or negative predictive values.

Figure 3
Figure 3
Image Tools

African-American patients comprised less than 10% of our cohort, and subgroup analyses here showed no notable differences. Furthermore, in an individual audit of 100 patients examined for the presence or absence of proteinuria before and during tenofovir DF therapy, we observed no changes in the presence of albuminuria as detected by dipstick. Fifteen patients died while receiving tenofovir DF; most of these individuals (64%) died secondary to sepsis. Importantly, tenofovir DF-induced renal failure was not a cause of death in any patient.

Back to Top | Article Outline

DISCUSSION

This cohort and case-controlled study demonstrates that renal failure associated with tenofovir DF is not more common than with other antiretroviral regimens. In 1058 individuals exposed to tenofovir DF, a maximum of 9 (<1%) patients developed an increased creatinine level without obvious other causes.

Although trials have reported no significant renal abnormalities in patients receiving tenofovir DF, including those coinfected with hepatitis B virus, isolated case reports have raised serious concerns regarding “renal safety”.18-21 These case reports have included patients recruited in the randomized 907 study, which investigated tenofovir DF in nucleoside-resistant HIV-1 infection.10 The investigators found that through week 24, the incidence of clinical adverse events was similar between patients receiving placebo and tenofovir DF (14% vs. 13%) and that this was maintained to week 48.

Our study illustrates that nonsignificant changes in creatinine after tenofovir DF exposure may occur (84 [8%] of 1058 patients exposed), although increases are usually associated with other causes of renal impairment and subsequent decreases in creatinine are observed. Interestingly, in 33 patients with a creatinine value greater than 120 μmol/L who were prescribed tenofovir DF, an increase in creatinine was not observed and tenofovir DF use was not associated with changes in dipstick-detectable proteinuria.

We found that antiretroviral-naive patients have a statistically significant increased creatinine level and an increased probability of developing an increased creatinine level during follow-up (P < 0.001). Although this may be related to other factors, including noncompliance, hepatitis C virus, and intravenous drug use, the finding is not surprising considering that studies have shown the renal epithelium may represent a specific compartment of HIV-1 replication. Here, in situ hybridization of renal biopsy tissue obtained from individuals with HIV-1 nephropathy suggests that the kidney represents a reservoir of HIV infection even in those patients with an undetectable viral load.24,25 The mechanism of in vivo replication in tissues such as the kidney remains unknown, and it also remains unclear whether HIV is truly latent here or whether it represents a slowly replicating pool that is relatively impervious to the effects of HAART.

Because most patients had concurrent reasons for renal dysfunction, it is not possible to attribute the change in creatinine clearance to tenofovir DF exposure alone. Although it is conceivable that tenofovir DF exposure increases the risk of a raised creatinine level in conjunction with other causes of renal nephrotoxicity, these data indicate that this is a generally rare occurrence or that the risk is no greater than with other NRTIs. As with other forms of antiretroviral therapy, idiosyncratic reactions to tenofovir DF have been documented. In our own cohort, the incidence of Fanconi syndrome is limited to 1 suspected case. Here, a 37-year-old man was receiving tenofovir DF therapy as well as zidovudine, didanosine, and delavirdine. He presented with a 2-day history of left ankle swelling, and a magnetic resonance imaging (MRI) scan revealed a stress fracture of the left distal tibia. Bone-derived alkaline phosphatase was measured at 301 IU/L, phosphate at 0.3 mmol/L, and calcium at 1.9 mmol/L. Urinalysis revealed the presence of glycosuria and aminoaciduria, and conservative management, including cessation of tenofovir DF, led to normalization of laboratory parameters. Since acceptance of this paper, we have had two further suspected cases of Fanconi Syndrome in our unit. Again, both patients had concurrent causes of renal dysfunction.

Patients with a raised creatinine level subsequent to receiving tenofovir DF should have other causes of nephrotoxicity eliminated. Although tenofovir DF may be associated with some renal pathologic findings, such events do not occur with an increased incidence in comparison to other antiretrovirals. These data also suggest that over time, such events may be less common in comparison to other regimens. Overall, receiving HAART is associated with improved renal function, as measured by creatinine levels, compared with not receiving HAART.

Back to Top | Article Outline

REFERENCES

1. Palella FJ Jr, Delaney KM, Moorman AC, et al. Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection. HIV Outpatient Study Investigators. N Engl J Med. 1998;338:853-860.

2. Hammer SM. Increasing choices for HIV therapy. N Engl J Med. 2002;346:2022-2023.

3. Cohen J. AIDS research. New drug shows promise in monkeys. Science. 1995;270:1121-1122.

4. Deeks SG, Barditch-Crovo P, Lietman PS, et al. Safety, pharmacokinetics, and antiretroviral activity of intravenous 9-[2-(R)-(phosphonomethoxy)propyl]adenine, a novel anti-human immunodeficiency virus (HIV) therapy, in HIV-infected adults. Antimicrob Agents Chemother. 1998;42:2380-2384.

5. De Clercq E. New developments in anti-HIV chemotherapy. Curr Med Chem. 2001;8:1543-1572.

6. Fung HB, Stone EA, Piacenti FJ. Tenofovir disoproxil fumarate: a nucleotide reverse transcriptase inhibitor for the treatment of HIV infection. Clin Ther. 2002;24:1515-1548.

7. Gallant JE, Deresinski S. Tenofovir disoproxil fumarate. Clin Infect Dis. 2003;37:944-950.

8. Walker UA. Update on mitochondrial toxicity: where are we now? J HIV Ther. 2003;8:32-35.

9. Margot NA, Isaacson E, McGowan I, et al. Genotypic and phenotypic analyses of HIV-1 in antiretroviral-experienced patients treated with tenofovir DF. AIDS. 2002;16:1227-1235.

10. Squires K, Pozniak AL, Pierone G Jr, et al. Tenofovir disoproxil fumarate in nucleoside-resistant HIV-1 infection: a randomized trial. Ann Intern Med. 2003;139:313-320.

11. Margot NA, Isaacson E, McGowan I, et al. Extended treatment with tenofovir disoproxil fumarate in treatment-experienced HIV-1-infected patients: genotypic, phenotypic, and rebound analyses. J Acquir Immune Defic Syndr. 2003;33:15-21.

12. Nunez M, Perez-Olmeda M, Diaz B, et al. Activity of tenofovir on hepatitis B virus replication in HIV-co-infected patients failing or partially responding to lamivudine. AIDS. 2002;16:2352-2354.

13. Nelson M, Portsmouth S, Stebbing J, et al. An open-label study of tenofovir in HIV-1 and hepatitis B virus co-infected individuals. AIDS. 2003;17(Suppl):F7-F10.

14. Benhamou Y, Tubiana R, Thibault V. Tenofovir disoproxil fumarate in patients with HIV and lamivudine-resistant hepatitis B virus. N Engl J Med. 2003;348:177-178.

15. Benhamou Y, Bochet M, Thibault V, et al. Safety and efficacy of adefovir dipivoxil in patients co-infected with HIV-1 and lamivudine-resistant hepatitis B virus: an open-label pilot study. Lancet. 2001;358:718-723.

16. Perazella MA. Drug-induced renal failure: update on new medications and unique mechanisms of nephrotoxicity. Am J Med Sci. 2003;325:349-362.

17. Ho ES, Lin DC, Mendel DB, et al. Cytotoxicity of antiviral nucleotides adefovir and cidofovir is induced by the expression of human renal organic anion transporter 1. J Am Soc Nephrol. 2000;11:383-393.

18. Verhelst D, Monge M, Meynard JL, et al. Fanconi syndrome and renal failure induced by tenofovir: a first case report. Am J Kidney Dis. 2002;40:1331-1333.

19. Creput C, Gonzalez-Canali G, Hill G, et al. Renal lesions in HIV-1-positive patient treated with tenofovir. AIDS. 2003;17:935-937.

20. Schaaf B, Aries SP, Kramme E, et al. Acute renal failure associated with tenofovir treatment in a patient with acquired immunodeficiency syndrome. Clin Infect Dis. 2003;37(Suppl):e41-e43.

21. Karras A, Lafaurie M, Furco A, et al. Tenofovir-related nephrotoxicity in human immunodeficiency virus-infected patients: three cases of renal failure, Fanconi syndrome, and nephrogenic diabetes insipidus. Clin Infect Dis. 2003;36:1070-1073.

22. Kimmel PL, Barisoni L, Kopp JB. Pathogenesis and treatment of HIV-associated renal diseases: lessons from clinical and animal studies, molecular pathologic correlations, and genetic investigations. Ann Intern Med. 2003;139:214-226.

23. Yeni PG, Hammer SM, Carpenter CC, et al. Antiretroviral treatment for adult HIV infection in 2002: updated recommendations of the International AIDS Society-USA Panel. JAMA. 2002;288:222-235.

24. Conaldi PG, Biancone L, Bottelli A, et al. HIV-1 kills renal tubular epithelial cells in vitro by triggering an apoptotic pathway involving caspase activation and Fas upregulation. J Clin Invest. 1998;102:2041-2049.

25. Marras D, Bruggeman LA, Gao F, et al. Replication and compartmentalization of HIV-1 in kidney epithelium of patients with HIV-associated nephropathy. Nat Med. 2002;8:522-526.

Cited By:

This article has been cited 66 time(s).

Clinical Infectious Diseases
Tenofovir-associated kidney diseases and interactions between tenofovir and other antiretrovirals
Lanzafame, M; Lattuada, E; Rapagna, F; Gottardi, M; Vento, S
Clinical Infectious Diseases, 42(): 1656-1657.

International Journal of Std & AIDS
The cost of antiretroviral drugs and influence on prescribing policies
Jones, R; Gazzard, B
International Journal of Std & AIDS, 17(8): 499-506.

Hiv Medicine
British HIV Association (BHIVA) guidelines for the treatment of HIV-infected adults with antiretroviral therapy (2006)
Gazzard, B
Hiv Medicine, 7(8): 487-503.

Clinical Infectious Diseases
Kidney Disease in Patients with HIV Infection and AIDS
Winston, J; Deray, G; Hawkins, T; Szczech, L; Wyatt, C; Young, B
Clinical Infectious Diseases, 47(): 1449-1457.
10.1086/593099
CrossRef
Hiv Medicine
Spectrum of chronic kidney disease in HIV-infected patients
Campbell, LJ; Ibrahim, F; Fisher, M; Holt, SG; Hendry, BM; Post, FA
Hiv Medicine, 10(6): 329-336.
10.1111/j.1468-1293.2008.00691.x
CrossRef
Methods and Findings in Experimental and Clinical Pharmacology
Gateways to clinical trials
Bayes, M; Rabasseda, X; Prous, JR
Methods and Findings in Experimental and Clinical Pharmacology, 27(2): 145-159.

Nephrology Dialysis Transplantation
Acute renal failure in HIV patients
Izzedine, H; Baumelou, A; Deray, G
Nephrology Dialysis Transplantation, 22(): 2757-2762.
10.1093/ndt/gfm404
CrossRef
American Journal of Kidney Diseases
Subclinical Tubular Injury in HIV-Infected Individuals on Antiretroviral Therapy: A Cross-sectional Analysis
Hall, AM; Edwards, SG; Lapsley, M; Connolly, JO; Chetty, K; O'Farrell, S; Unwin, RJ; Williams, IG
American Journal of Kidney Diseases, 54(6): 1034-1042.
10.1053/j.ajkd.2009.07.012
CrossRef
Nature Reviews Nephrology
The nephrotoxic effects of HAART
Izzedine, H; Harris, M; Perazella, MA
Nature Reviews Nephrology, 5(): 564-574.
10.1038/nrneph.2009.142
CrossRef
Nephrology
Review article: Hepatitis B and dialysis
Edey, M; Barraclough, K; Johnson, DW
Nephrology, 15(2): 137-145.
10.1111/j.1440-1797.2009.01268.x
CrossRef
Biomedicine & Pharmacotherapy
Tenofovir renal safety in HIV-infected patients: Results from the SCOLTA project
Madeddu, G; Bonfant, P; De Socio, GV; Carradori, S; Grosso, C; Marconi, P; Penco, G; Rosella, E; Miccolis, S; Melzi, S; Mura, MS; Landonio, S; Ricci, E; Quirino, T
Biomedicine & Pharmacotherapy, 62(1): 6-11.
10.1016/j.biopha.2007.04.008
CrossRef
Clinical Journal of the American Society of Nephrology
Highly active antiretroviral therapy and the kidney: An update on antiretroviral medications for nephrologists
Berns, JS; Kasbekar, N
Clinical Journal of the American Society of Nephrology, 1(1): 117-129.
10.2215/CJN.00370705
CrossRef
AIDS Patient Care and Stds
Tenofovir-associated Fanconi syndrome: Review of the FDA adverse event reporting system
Gupta, SK
AIDS Patient Care and Stds, 22(2): 99-103.
10.1089/apc.2007.0052
CrossRef
Biochemical Pharmacology
Acyclic nucleoside phosphonates: Past, present and future - Bridging chemistry to HIV, HBV, HCV, HPV, adeno-, herpes-, and poxvirus infections: The phosphonate bridge
De Clercq, E
Biochemical Pharmacology, 73(7): 911-922.
10.1016/j.bcp.2006.09.014
CrossRef
Enfermedades Infecciosas Y Microbiologia Clinica
Acute renal failure associated with the use of tenofovir combined with atazanavir in patients with HIV infection
Vallecillo-Sanchez, G; Guelar-Grimberg, A; Gonzalez-Mena, A; Knobel-Freud, H
Enfermedades Infecciosas Y Microbiologia Clinica, 26(5): 316-317.

Clinical Infectious Diseases
Long-Term Evolution and Determinants of Renal Function in HIV-Infected Patients Who Began Receiving Combination Antiretroviral Therapy in 1997-1999, ANRS CO8 APROCO-COPILOTE
Leport, C; Bouteloup, V; Rossert, J; Garre, M; Iordache, L; Dellamonica, P; Herson, S; Raffi, F; Chene, G
Clinical Infectious Diseases, 49(): 1950-1954.
10.1086/648445
CrossRef
Expert Opinion on Drug Safety
Tenofovir-induced kidney injury
Gitman, MD; Hirschwerk, D; Baskin, CH; Singhal, PC
Expert Opinion on Drug Safety, 6(2): 155-164.
10.1517/14740338.6.2.155
CrossRef
Hiv Clinical Trials
The safety and efficacy of tenofovir DF in combination with lamivudine and efavirenz through 6 years in antiretroviral-naive HIV-1-infected patients
Cassetti, I; Madruga, JVR; Suleiman, JMAH; Etzel, A; Zhong, LJ; Cheng, AK; Enejosa, J
Hiv Clinical Trials, 8(3): 164-172.
10.1310/hct0803-164
CrossRef
Hiv Clinical Trials
The safety and efficacy of switching stavuldine to tenofovir DF in combination with lamivudine and efavirenz in HIV-1-infected patients: Three-year follow-up after switching therapy
Madruga, JVR; Cassetti, I; Suleiman, JMAH; Etzel, A; Zhong, L; Holmes, CB; Cheng, AK; Enejosa, J
Hiv Clinical Trials, 8(6): 381-390.
10.1310/hct0806-381
CrossRef
AIDS
The safety of tenofovir disoproxil fumarate for the treatment of HIV infection in adults: the first 4 years
Nelson, MR; Katlama, C; Montaner, JS; Cooper, DA; Gazzard, B; Clotet, B; Lazzari, A; Schewe, K; Lange, J; Wyatt, C; Curtis, S; Chen, SS; Smith, S; Bischofberger, N; Rooney, JF
AIDS, 21(): 1273-1281.

International Journal of Clinical Practice
Tenofovir: what have over 1 million years of patient experience taught us?
Pozniak, A
International Journal of Clinical Practice, 62(8): 1285-1293.
10.1111/j.1742-1241.2008.01817.x
CrossRef
Hiv Medicine
Factors associated with renal dysfunction within an urban HIV-infected cohort in the era of highly active antiretroviral therapy
Overton, ET; Nurutdinova, D; Freeman, J; Seyfried, W; Mondy, KE
Hiv Medicine, 10(6): 343-350.
10.1111/j.1468-1293.2009.00693.x
CrossRef
Drugs
Tenofovir disoproxil fumarate - A review of its use in the management of HIV infection
Lyseng-Williamson, KA; Reynolds, NA; Plosker, GL
Drugs, 65(3): 413-432.

Antiviral Therapy
Exploring mitochondrial nephrotoxicity as a potential mechanism of kidney dysfunction among HIV-infected patients on highly active antiretroviral therapy
Cote, HCF; Magil, AB; Harris, M; Scarth, BJ; Gadawski, I; Wang, N; Yu, E; Yip, B; Zalunardo, N; Werb, R; Hogg, R; Harrigan, PR; Montaner, JS
Antiviral Therapy, 11(1): 79-86.

Hiv Medicine
British HIV Association guidelines for the treatment of HIV-1-infected adults with antiretroviral therapy 2008
Gazzard, BG
Hiv Medicine, 9(8): 563-608.
10.1111/j.1468-1293.2008.00636.x
CrossRef
Journal of General Internal Medicine
Acquired Fanconi's syndrome associated with tenofovir therapy
Mathew, G; Knaus, SJ
Journal of General Internal Medicine, 21(): C3-C5.
10.1111/j.1525-1497.2006.00518.x
CrossRef
Mayo Clinic Proceedings
HIV-1 infection and the kidney: An evolving challenge in HIV medicine
De Silva, TI; Post, FA; Griffin, MD; Dockrell, DH
Mayo Clinic Proceedings, 82(9): 1103-1116.

Antiviral Research
The frequency and reasons for antiretroviral switching with specific antiretroviral associations: The SWITCH study
Davidson, I; Beardsell, H; Smith, B; Mandalia, S; Bower, M; Gazzard, B; Nelson, M; Stebbing, J
Antiviral Research, 86(2): 227-229.
10.1016/j.antiviral.2010.03.001
CrossRef
Clinical Drug Investigation
Renal safety of tenofovir in HIV-infected children - A prospective, 96-week longitudinal study
Vigano, A; Zuccotti, GV; Martelli, L; Giacomet, V; Cafarelli, L; Borgonovo, S; Beretta, S; Rombola, G; Mora, S
Clinical Drug Investigation, 27(8): 573-581.

Antimicrobial Agents and Chemotherapy
Chronic administration of tenofovir to rhesus macaques from infancy through adulthood and pregnancy: Summary of pharmacokinetics and biological and virological effects
Van Rompay, KKA; Durand-Gasselin, L; Brignolo, LL; Ray, AS; Abel, K; Cihlar, T; Spinner, A; Jerome, C; Moore, J; Kearney, BP; Marthas, ML; Reiser, H; Bischofberger, N
Antimicrobial Agents and Chemotherapy, 52(9): 3144-3160.
10.1128/AAC.00350-08
CrossRef
Revue De Medecine Interne
Acute renal failure, Fanconi syndrome and insipidus diabetes in a HIV-infected patient treated with Tenofovir
Harmouche, H; Le Bras, P; Bignani, O; Delfraissey, JF; Goujard, C
Revue De Medecine Interne, 26(6): 522-523.
10.1016/j.revmed.2005.01.013
CrossRef
Journal of Antimicrobial Chemotherapy
Glomerular filtration rates in HIV-infected patients treated with and without tenofovir: a prospective, observational study
Guaraldi, G; Roverato, A; Giovanardi, C; Ravera, F; Squillace, N; Orlando, G; Cappelli, G; Esposito, R; Palella, F
Journal of Antimicrobial Chemotherapy, 63(2): 374-379.
10.1093/jac/dkn499
CrossRef
AIDS Patient Care and Stds
Prevalence and Factors Associated with Renal Dysfunction Among HIV-Infected Patients
Crum-Cianflone, N; Ganesan, A; Teneza-Mora, N; Riddle, M; Medina, S; Barahona, I; Brodine, S
AIDS Patient Care and Stds, 24(6): 353-360.
10.1089/apc.2009.0326
CrossRef
Hiv Medicine
Minor changes in calculated creatinine clearance and anion-gap are associated with tenofovir disoproxil fumarate-containing highly active antiretroviral therapy
Winston, A; Amin, J; Mallon, PWG; Marriott, D; Carr, A; Cooper, DA; Emery, S
Hiv Medicine, 7(2): 105-111.

Expert Opinion on Drug Safety
Cardiovascular & renal - Antiretroviral therapy and the kidney: balancing benefit and risk in patients with HIV infection
Wyatt, CM; Klotman, PE
Expert Opinion on Drug Safety, 5(2): 275-287.
10.1517/14740338.5.2.275
CrossRef
Journal of Infectious Diseases
Toward a pharmacogenetic understanding of nucleotide and nucleoside analogue toxicity
Hulgan, T; Haas, DW
Journal of Infectious Diseases, 194(): 1471-1474.

Advances in Chronic Kidney Disease
Nephrotoxicity as a complication of antiretroviral therapy
Valle, R; Haragsim, L
Advances in Chronic Kidney Disease, 13(3): 314-319.
10.1053/j.ackd.2006.04.017
CrossRef
Renal Failure
Acute renal failure after initiation of tenofovir disoproxil fumarate
Hynes, P; Urbina, A; McMeeking, A; Barisoni, L; Rabenou, R
Renal Failure, 29(8): 1063-1066.
10.1080/08860220701643831
CrossRef
Antiviral Therapy
Tenofovir use is associated with a reduction in calculated glomerular filtration rates in the Swiss HIV Cohort Study
Fux, CA; Simcock, M; Wolbers, M; Bucher, HC; Hirschel, B; Oprovil, M; Vernazza, P; Cavassini, M; Bernasconi, E; Elzi, L; Furrer, H
Antiviral Therapy, 12(8): 1165-1173.

Journal of Viral Hepatitis
Reduced glomerular filtration rate but sustained virologic response in HIV/hepatitis B co-infected individuals on long-term tenofovir
Tan, LKK; Gilleece, Y; Mandalia, S; Murungi, A; Grover, D; Fisher, M; Atkins, M; Nelson, M
Journal of Viral Hepatitis, 16(7): 471-478.
10.1111/j.1365-2893.2009.01084.x
CrossRef
Clinical Infectious Diseases
Changes in renal function associated with tenofovir disoproxil fumarate treatment, compared with nucleoside reverse-transcriptase inhibitor treatment
Gallant, JE; Parish, MA; Keruly, JC; Moore, RD
Clinical Infectious Diseases, 40(8): 1194-1198.

Expert Opinion on Drug Safety
Nephrotoxicity associated with antiretroviral therapy in HIV-infected patients
Harris, M
Expert Opinion on Drug Safety, 7(4): 389-400.
10.1517/14740330802211423
CrossRef
Expert Opinion on Pharmacotherapy
Experience with tenofovir disoproxil fumarate for antiretroviral therapy
Stephan, C
Expert Opinion on Pharmacotherapy, 9(7): 1197-1209.
10.1517/14656560802012338
CrossRef
Journal of Infection
Is tenofovir involved in hypophosphatemia and decrease of tubular phosphate reabsorption in HIV-positive adults?
Badiou, S; De Boever, CM; Terrier, N; Baillat, V; Cristol, JP; Reynes, J
Journal of Infection, 52(5): 335-338.
10.1016/j.jinf.2005.07.020
CrossRef
AIDS
A randomized comparative trial of tenofovir DF or abacavir as replacement for a thymidine analogue in persons with lipoatrophy
Moyle, GJ; Sabin, CA; Cartledge, J; Johnson, M; Wilkins, E; Churchill, D; Hay, P; Fakoya, A; Murphy, M; Scullard, G; Leen, C; Reilly, G
AIDS, 20(): 2043-2050.

AIDS Reader
Renal safety of tenofovir disoproxil fumarate
Sax, PE; Gallant, JE; Klotman, PE
AIDS Reader, 17(2): 90-+.

Hiv Clinical Trials
Serious renal impairment occurs rarely with use of tenofovir
Scott, JD; Wolfe, PR; Bolan, RK; Guyer, B
Hiv Clinical Trials, 7(2): 55-58.

Enfermedades Infecciosas Y Microbiologia Clinica
Assessment and management of kidney disease in the HIV-1-infected patient. A practical review
Domingo, P; Knobel, H; Gutierrez, F; Barril, G; Fulladosa, X
Enfermedades Infecciosas Y Microbiologia Clinica, 28(3): 185-198.
10.1016/j.eimc.2009.05.004
CrossRef
AIDS Patient Care and Stds
Low frequency of renal function impairment during one-year of therapy with tenofovir-containing regimens in the real-world: A case-control study
Padilla, S; Gutierrez, F; Masia, M; Canovas, VC; Orozco, C
AIDS Patient Care and Stds, 19(7): 421-424.

Journal of Hepatology
Treatment of viral hepatitis in HIV-coinfected patients-adverse events and their management
Mauss, S
Journal of Hepatology, 44(): S114-S118.
10.1016/j.jhep.2005.11.024
CrossRef
Clinical Infectious Diseases
HIV-associated renal diseases and highly active antiretroviral therapy-induced nephropathy
Roling, J; Schmid, H; Fischereder, M; Draenert, R; Goebel, FD
Clinical Infectious Diseases, 42(): 1488-1495.

International Journal of Clinical Practice
Renal complications in HIV
Jones, R; Scott, C; Nelson, M; Levy, J
International Journal of Clinical Practice, 61(6): 991-998.
10.1111/j.1742-1241.2007.01376.x
CrossRef
Journal of Antimicrobial Chemotherapy
No change in calculated creatinine clearance after tenofovir initiation among Thai patients
Gayet-Ageron, A; Ananworanich, J; Jupimai, T; Chetchotisakd, P; Prasithsirikul, W; Ubolyam, S; Le Braz, M; Ruxrungtham, K; Rooney, JF; Hirschel, B
Journal of Antimicrobial Chemotherapy, 59(5): 1034-1037.
10.1093/jac/dkm064
CrossRef
Clinical Infectious Diseases
Severe renal dysfunction and risk factors associated with renal impairment in HIV-infected adults in Africa initiating antiretroviral therapy
Reid, A; Stoehr, W; Walker, AS; Williams, IG; Kityo, C; Hughes, P; Kambugu, A; Gilks, CF; Mugyenyi, P; Munderi, P; Hakim, J; Gibb, DM
Clinical Infectious Diseases, 46(8): 1271-1281.
10.1086/533468
CrossRef
Journal of Antimicrobial Chemotherapy
Adherence to trizivir and tenofovir as a simplified salvage regimen is associated with suppression of viraemia and a decreased cholesterol
Latham, V; Stebbing, J; Mandalia, S; Michailidis, C; Davies, E; Bower, M; Gazzard, B; Nelson, M
Journal of Antimicrobial Chemotherapy, 56(1): 186-189.
10.1093/jac/dki170
CrossRef
Expert Opinion on Drug Safety
Renal toxicity associated with tenofovir use
Rodriguez-Novoa, S; Alvarez, E; Labarga, P; Soriano, V
Expert Opinion on Drug Safety, 9(4): 545-559.
10.1517/14740331003627458
CrossRef
Pediatric Nephrology
Update on tenofovir toxicity in the kidney
Hall, AM
Pediatric Nephrology, 28(7): 1011-1023.
10.1007/s00467-012-2269-7
CrossRef
AIDS
Response to Blaas et al., ‘Acute renal failure in HIV patients with liver cirrhosis receiving tenofovir: a report of two cases’
Ranneberg, B; Mertenskoetter, T; Pearce, G
AIDS, 21(6): 783.
10.1097/QAD.0b013e3280b077a6
PDF (349) | CrossRef
AIDS
The 3-year renal safety of a tenofovir disoproxil fumarate vs. a thymidine analogue-containing regimen in antiretroviral-naive patients
Gallant, JE; Winston, JA; DeJesus, E; Pozniak, AL; Chen, S; Cheng, AK; Enejosa, JV
AIDS, 22(16): 2155-2163.
10.1097/QAD.0b013e3283112b8e
PDF (246) | CrossRef
JAIDS Journal of Acquired Immune Deficiency Syndromes
Renal Safety of Tenofovir Disoproxil Fumarate in HIV-1 Treatment-experienced Patients with Adverse Events Related to Prior NRTI Use: Data from a Prospective, Observational, Multicenter Study
Moreno, S; Domingo, P; Palacios, R; Santos, J; Falcó, V; Murillas, J; Estrada, V; Ena, J; Alvarez, M; Recover Study Group,
JAIDS Journal of Acquired Immune Deficiency Syndromes, 42(3): 385-387.
10.1097/01.qai.0000221690.54349.83
PDF (283) | CrossRef
JAIDS Journal of Acquired Immune Deficiency Syndromes
A Randomized Comparative Trial of Continued Zidovudine/Lamivudine or Replacement With Tenofovir Disoproxil Fumarate/Emtricitabine in Efavirenz-Treated HIV-1-Infected Individuals
Fisher, M; Moyle, GJ; Shahmanesh, M; Orkin, C; Kingston, M; Wilkins, E; Ewan, J; Liu, H; Ebrahimi, R; Reilly, G; for the SWEET (Simplification With Easier Emtricitabine Tenofovir) group UK,
JAIDS Journal of Acquired Immune Deficiency Syndromes, 51(5): 562-568.
10.1097/QAI.0b013e3181ae2eb9
PDF (234) | CrossRef
JAIDS Journal of Acquired Immune Deficiency Syndromes
Evaluation of a Systematic Substitution of Zidovudine for Stavudine-Based HAART in a Program Setting in Rural Cambodia
Isaakidis, P; Raguenaud, M; Phe, T; Khim, SA; Kuoch, S; Khem, S; Reid, T; Arnould, L
JAIDS Journal of Acquired Immune Deficiency Syndromes, 49(1): 48-54.
10.1097/QAI.0b013e31817bec19
PDF (129) | CrossRef
AIDS
Serum creatinine changes in HIV-seropositive patients receiving tenofovir
El Sahly, HM; Teeter, L; Zerai, T; Andrade, RA; Munoz, C; Nnabuife, C; Hunter, R
AIDS, 20(5): 786-787.
10.1097/01.aids.0000216386.60481.47
PDF (928) | CrossRef
JAIDS Journal of Acquired Immune Deficiency Syndromes
Impact of Tenofovir on Renal Function in HIV-Infected, Antiretroviral-Naive Patients
Horberg, M; Tang, B; Towner, W; Silverberg, M; Bersoff-Matcha, S; Hurley, L; Chang, J; Blank, J; Quesenberry, C; Klein, D
JAIDS Journal of Acquired Immune Deficiency Syndromes, 53(1): 62-69.
10.1097/QAI.0b013e3181be6be2
PDF (256) | CrossRef
JAIDS Journal of Acquired Immune Deficiency Syndromes
Chronic Kidney Disease Prevalence and Risk Factors Among HIV-Infected Patients
Sorlí, ML; Guelar, A; Montero, M; González, A; Rodriguez, E; Knobel, H
JAIDS Journal of Acquired Immune Deficiency Syndromes, 48(4): 506-508.
10.1097/QAI.0b013e31817bbecb
PDF (54) | CrossRef
JAIDS Journal of Acquired Immune Deficiency Syndromes
Evaluation of Oral Tenofovir Disoproxil Fumarate and Topical Tenofovir GS-7340 to Protect Infant Macaques Against Repeated Oral Challenges With Virulent Simian Immunodeficiency Virus
Van Rompay, KK; Kearney, BP; Sexton, JJ; Colón, R; Lawson, JR; Blackwood, EJ; Lee, WA; Bischofberger, N; Marthas, ML
JAIDS Journal of Acquired Immune Deficiency Syndromes, 43(1): 6-14.
10.1097/01.qai.0000224972.60339.7c
PDF (289) | CrossRef
Back to Top | Article Outline
Keywords:

tenofovir DF; highly active antiretroviral therapy; renal; cohort; creatinine

© 2004 Lippincott Williams & Wilkins, Inc.

Login

Search for Similar Articles
You may search for similar articles that contain these same keywords or you may modify the keyword list to augment your search.