Discontinuation and Dose Adjustment of Tenofovir in HIV Patients with Impaired Renal Function
DOI:
https://doi.org/10.12970/2309-0529.2013.01.02.4Keywords:
HIV, tenofovir, renal function, clinical handling.Abstract
Background: Impaired renal function is a major concern in HIV-infected patients treated with tenofovir. We undertook this study to clarify how reduced renal function in patients on tenofovir treatment is handled in routine clinical practice. Methods: From a population-based cohort of Danish HIV patients we identified all patients who started tenofovir for the first time and estimated relative risk (RR) of discontinuation of tenofovir in relation to baseline and last estimated glomerular filtration rate (eGFR, measured in ml/min per 1.73 m2). For patients who for the first time had eGFR<50, we calculated time to the combined endpoint of eGFR>50 or stop or dose modification. Results: 2,066 patients were included in the study. Patients with last eGFR<65 had increased risk of stopping tenofovir and the risk increased with decreasing eGFR (eGFR 60-65: adjusted RR 2.1; eGFR <50: adjusted RR 8.1). We identified 115 patients with eGFR<50. After 1 year only 12.3% were still on standard dose tenofovir and had eGFR<50. Conclusion: This study demonstrates that tenofovir treatment is stopped rapidly in patients who develop renal impairment. Patients with a normal baseline renal function have a low risk of treatment modification.References
[1] Rling J, Schmid H, Fischereder M, Draenert R, Goebel FD. HIV-associated renal diseases and highly active antiretroviral therapy-induced nephropathy. Clin Infect Dis 2006; 42: 1488- 95. http://dx.doi.org/10.1086/503566
[2] Brewster U, Perazella M. Acute interstitial nephritis associated with atazanavir, a new protease inhibitor. Am J Kidney Dis 2004; 44: e81-4.
[3] Eira M, Araujo M, Seguro AC. Urinary NO3 excretion and renal failure in indinavir-treated patients. Braz J Med Biol Res 2006; 39: 1065-70. http://dx.doi.org/10.1590/S0100-879X2006000800009
[4] Schmid S, Opravil M, Moddel M, et al. Acute interstitial nephritis of HIV-positive patients under atazanavir and tenofovir therapy in a retrospective analysis of kidney biopsies. Virchows Arch 2007; 450: 665-70. http://dx.doi.org/10.1007/s00428-007-0418-3
[5] Choi AI, Shlipak MG, Hunt PW, Martin JN, Deeks SG. HIVinfected persons continue to lose kidney function despite successful antiretroviral therapy. AIDS 2009; 16: 2143-9. http://dx.doi.org/10.1097/QAD.0b013e3283313c91
[6] Kalayjian RC, Lau B, Mechekano RN, et al. Risk factors for chronic kidney disease in a large cohort of HIV-1 infected individuals initiating antiretroviral therapy in routine care. AIDS 2012; 15: 1907-15. http://dx.doi.org/10.1097/QAD.0b013e328357f5ed
[7] Laprise C, Baril JG, Dufresne S, Trottier H. Association between tenofovir exposure and reduced kidney function in a cohort of HIV-positiv patients: results from 10 years of followup. Clin Infect Dis 2013; 56: 567-75. http://dx.doi.org/10.1093/cid/cis937
[8] Hall AM. Update on tenofovir toxicity in the kidney. Pediatr Nephrol 2013; 28: 1011-23. http://dx.doi.org/10.1007/s00467-012-2269-7
[9] Ryom L, Mocroft A, Kirk O, et al. Association between antiretroviral exposure and renal impairment among HIVpositiv persons with normal baseline renal function: the D:A:D study. J Infect Dis 2013; 207: 1359-69. http://dx.doi.org/10.1093/infdis/jit043
[10] (SPC, EMA) http://apps.who.int/prequal/whopar/whoparproducts/HA417part4v1.pdf.
[11] Lohse N, Hansen AB, Jensen-Fangel S, et al. Demographics of HIV-1 infection in Denmark: results from the Danish HIV Cohort Study. Scand J Infect Dis 2005; 37: 338-43. http://dx.doi.org/10.1080/00365540510031692
[12] Levey A, Coresh J, GreeneT, et al. Using standardized serum creatinine values in the modification of diet in renal disease study equation for estimating glomerular filtration rate. Ann Intern Med 2006; 145: 247-54. http://dx.doi.org/10.7326/0003-4819-145-4-200608150- 00004
[13] Poizot-Martin I, Solas C, Allemand J, et al. Renal impairment in patients receiving a tenofovir-cART regimen: Impact of tenofovir trough concentration. J Acquir Immune Defic Syndr 2012; 62: 375-80. http://dx.doi.org/10.1097/QAI.0b013e31827ce4ee
[14] Rasch MG, Engsig FN, Feldt-Rasmussen B, et al. Renal function and incidence of chronic kidney disease in HIV patients: a Danish cohort study. Scand J Infect Dis 2012; 44: 689-96. http://dx.doi.org/10.3109/00365548.2012.673730
[15] Rasch MG, Helleberg M, Feldt-Rasmussen B, et al. Increased risk of dialysis and end stage renal disease among HIV patients in Denmark compared to the background population. Nephrol Dial Transplant 2013 Aug 24. [Epub ahead of print] http://dx.doi.org/10.1093/ndt/gft289
[16] Langness JA, Hindman JT, Johnson SC, Kiser JJ. The frequency of adjusted renal dosing of tenofovir DF and its effects on patients outcome. J Pharm Pract 2013; 26: 397- 400. http://dx.doi.org/10.1177/0897190012465986