Objective To compare the rate of decline of renal function in tenofovir- and abacavir-based antiretroviral therapy (ART) in low-body weight treatment-na？ve patients with HIV infection. Design We conducted a single-center retrospective cohort study of 503 Japanese patients who commenced on either tenofovir- or abacavir-based initial ART. Methods The incidence of renal dysfunction, defined as more than 25% fall in estimated glomerular filtration rate (eGFR) from the baseline, was determined in each group. The effect of tenofovir on renal dysfunction was estimated by univariate and multivariate Cox hazards models as the primary exposure. Changes in eGFR until 96 weeks were estimated in both groups with a repeated measures mixed model. Results The median body weight of the cohort was 64 kg. The estimated incidence of renal dysfunction in the tenofovir and the abacavir arm was 9.84 per 100 and 4.55 per 100 person-years, respectively. Tenofovir was significantly associated with renal dysfunction by univariate and multivariate analysis (HR = 1.747; 95% CI, 1.152–2.648; p = 0.009) (adjusted HR = 2.080; 95% CI, 1.339–3.232; p<0.001). In subgroup analysis of the patients stratified by intertertile baseline body weight, the effect of tenofovir on renal dysfunction was more evident in patients with lower baseline body weight by multivariate analysis (≤60 kg: adjusted HR = 2.771; 95%CI, 1.494–5.139; p = 0.001) (61–68 kg: adjusted HR = 1.908; 95%CI, 0.764–4.768; p = 0.167) (>68 kg: adjusted HR = 0.997; 95%CI, 0.318–3.121; p = 0.995). The fall in eGFR was significantly greater in the tenofovir arm than the abacavir arm after starting ART (p = 0.003). Conclusion The incidence of renal dysfunction in low body weight patients treated with tenofovir was twice as high as those treated with abacavir. Close monitoring of renal function is recommended for patients with small body weight especially those with baseline body weight <60 kg treated with tenofovir.
References
[1]
Mallal S, Phillips E, Carosi G, Molina JM, Workman C, et al. (2008) HLA-B*5701 screening for hypersensitivity to abacavir. N Engl J Med 358: 568–579.
[2]
Sax PE, Tierney C, Collier AC, Fischl MA, Mollan K, et al. (2009) Abacavir-lamivudine versus tenofovir-emtricitabine for initial HIV-1 therapy. N Engl J Med 361: 2230–2240.
[3]
Peyriere H, Reynes J, Rouanet I, Daniel N, de Boever CM, et al. (2004) Renal tubular dysfunction associated with tenofovir therapy: report of 7 cases. J Acquir Immune Defic Syndr 35: 269–273.
[4]
Verhelst D, Monge M, Meynard JL, Fouqueray B, Mougenot B, et al. (2002) Fanconi syndrome and renal failure induced by tenofovir: a first case report. Am J Kidney Dis 40: 1331–1333.
[5]
Winston A, Amin J, Mallon P, Marriott D, Carr A, et al. (2006) Minor changes in calculated creatinine clearance and anion-gap are associated with tenofovir disoproxil fumarate-containing highly active antiretroviral therapy. HIV Med 7: 105–111.
[6]
Fux CA, Simcock M, Wolbers M, Bucher HC, Hirschel B, et al. (2007) Tenofovir use is associated with a reduction in calculated glomerular filtration rates in the Swiss HIV Cohort Study. Antivir Ther 12: 1165–1173.
[7]
Gallant JE, Winston JA, DeJesus E, Pozniak AL, Chen SS, et al. (2008) The 3-year renal safety of a tenofovir disoproxil fumarate vs. a thymidine analogue-containing regimen in antiretroviral-naive patients. AIDS 22: 2155–2163.
[8]
Kinai E, Hanabusa H (2009) Progressive renal tubular dysfunction associated with long-term use of tenofovir DF. AIDS Res Hum Retroviruses 25: 387–394.
[9]
Cooper RD, Wiebe N, Smith N, Keiser P, Naicker S, et al. (2010) Systematic review and meta-analysis: renal safety of tenofovir disoproxil fumarate in HIV-infected patients. Clin Infect Dis 51: 496–505.
[10]
Post FA, Moyle GJ, Stellbrink HJ, Domingo P, Podzamczer D, et al. (2010) Randomized comparison of renal effects, efficacy, and safety with once-daily abacavir/lamivudine versus tenofovir/emtricitabine, administered with efavirenz, in antiretroviral-naive, HIV-1-infected adults: 48-week results from the ASSERT study. J Acquir Immune Defic Syndr 55: 49–57.
[11]
Smith KY, Patel P, Fine D, Bellos N, Sloan L, et al. (2009) Randomized, double-blind, placebo-matched, multicenter trial of abacavir/lamivudine or tenofovir/emtricitabine with lopinavir/ritonavir for initial HIV treatment. AIDS 23: 1547–1556.
[12]
Gayet-Ageron A, Ananworanich J, Jupimai T, Chetchotisakd P, Prasithsirikul W, et al. (2007) No change in calculated creatinine clearance after tenofovir initiation among Thai patients. J Antimicrob Chemother 59: 1034–1037.
[13]
Chaisiri K, Bowonwatanuwong C, Kasettratat N, Kiertiburanakul S (2010) Incidence and risk factors for tenofovir-associated renal function decline among Thai HIV-infected patients with low-body weight. Curr HIV Res 8: 504–509.
[14]
Reid A, Stohr W, Walker AS, Williams IG, Kityo C, et al. (2008) Severe renal dysfunction and risk factors associated with renal impairment in HIV-infected adults in Africa initiating antiretroviral therapy. Clin Infect Dis 46: 1271–1281.
[15]
Gatanaga H, Tachikawa N, Kikuchi Y, Teruya K, Genka I, et al. (2006) Urinary beta2-microglobulin as a possible sensitive marker for renal injury caused by tenofovir disoproxil fumarate. AIDS Res Hum Retroviruses 22: 744–748.
[16]
Nishijima T, Komatsu H, Gatanaga H, Aoki T, Watanabe K, et al. (2011) Impact of Small Body Weight on Tenofovir-Associated Renal Dysfunction in HIV-Infected Patients: A Retrospective Cohort Study of Japanese Patients. PLoS One 6: e22661.
[17]
Bygrave H, Kranzer K, Hilderbrand K, Jouquet G, Goemaere E, et al. (2011) Renal safety of a tenofovir-containing first line regimen: experience from an antiretroviral cohort in rural Lesotho. PLoS One 6: e17609.
[18]
De Beaudrap P, Diallo MB, Landman R, Gueye NF, Ndiaye I, et al. (2010) Changes in the renal function after tenofovir-containing antiretroviral therapy initiation in a Senegalese cohort (ANRS 1215). AIDS Res Hum Retroviruses 26: 1221–1227.
[19]
Brennan A, Evans D, Maskew M, Naicker S, Ive P, et al. (2011) Relationship between renal dysfunction, nephrotoxicity and death among HIV adults on tenofovir. AIDS 25: 1603–1609.
[20]
Bash LD, Coresh J, Kottgen A, Parekh RS, Fulop T, et al. (2009) Defining incident chronic kidney disease in the research setting: The ARIC Study. Am J Epidemiol 170: 414–424.
[21]
Chue CD, Edwards NC, Davis LJ, Steeds RP, Townend JN, et al. (2011) Serum phosphate but not pulse wave velocity predicts decline in renal function in patients with early chronic kidney disease. Nephrol Dial Transplant.
[22]
Levey AS, Coresh J, Greene T, Stevens LA, Zhang YL, et al. (2006) Using standardized serum creatinine values in the modification of diet in renal disease study equation for estimating glomerular filtration rate. Ann Intern Med 145: 247–254.
[23]
Gupta SK, Eustace JA, Winston JA, BoydstunII , Ahuja TS, et al. (2005) Guidelines for the management of chronic kidney disease in HIV-infected patients: recommendations of the HIV Medicine Association of the Infectious Diseases Society of America. Clin Infect Dis 40: 1559–1585.
[24]
Goicoechea M, Liu S, Best B, Sun S, Jain S, et al. (2008) Greater tenofovir-associated renal function decline with protease inhibitor-based versus nonnucleoside reverse-transcriptase inhibitor-based therapy. J Infect Dis 197: 102–108.
[25]
Nelson MR, Katlama C, Montaner JS, Cooper DA, Gazzard B, et al. (2007) The safety of tenofovir disoproxil fumarate for the treatment of HIV infection in adults: the first 4 years. AIDS 21: 1273–1281.
[26]
Garrow JS, Webster J (1985) Quetelet's index (W/H2) as a measure of fatness. Int J Obes 9: 147–153.
[27]
Cockcroft DW, Gault MH (1976) Prediction of creatinine clearance from serum creatinine. Nephron 16: 31–41.
[28]
Gallant JE, Moore RD (2009) Renal function with use of a tenofovir-containing initial antiretroviral regimen. AIDS 23: 1971–1975.
[29]
Bedimo RJ, Westfall AO, Drechsler H, Vidiella G, Tebas P (2011) Abacavir use and risk of acute myocardial infarction and cerebrovascular events in the highly active antiretroviral therapy era. Clin Infect Dis 53: 84–91.
[30]
Nolan D, Gaudieri S, Mallal S (2003) Pharmacogenetics: a practical role in predicting antiretroviral drug toxicity? J HIV Ther 8: 36–41.
[31]
Sun HY, Hung CC, Lin PH, Chang SF, Yang CY, et al. (2007) Incidence of abacavir hypersensitivity and its relationship with HLA-B*5701 in HIV-infected patients in Taiwan. J Antimicrob Chemother 60: 599–604.
[32]
Gatanaga H, Honda H, Oka S (2008) Pharmacogenetic information derived from analysis of HLA alleles. Pharmacogenomics 9: 207–214.
[33]
Kohler JJ, Hosseini SH, Hoying-Brandt A, Green E, Johnson DM, et al. (2009) Tenofovir renal toxicity targets mitochondria of renal proximal tubules. Lab Invest 89: 513–519.
[34]
Post FA, Holt SG (2009) Recent developments in HIV and the kidney. Curr Opin Infect Dis 22: 43–48.
[35]
Jullien V, Treluyer JM, Rey E, Jaffray P, Krivine A, et al. (2005) Population pharmacokinetics of tenofovir in human immunodeficiency virus-infected patients taking highly active antiretroviral therapy. Antimicrob Agents Chemother 49: 3361–3366.
[36]
Van Rompay KK, Durand-Gasselin L, Brignolo LL, Ray AS, Abel K, et al. (2008) Chronic administration of tenofovir to rhesus macaques from infancy through adulthood and pregnancy: summary of pharmacokinetics and biological and virological effects. Antimicrob Agents Chemother 52: 3144–3160.
[37]
Kiser JJ, Fletcher CV, Flynn PM, Cunningham CK, Wilson CM, et al. (2008) Pharmacokinetics of antiretroviral regimens containing tenofovir disoproxil fumarate and atazanavir-ritonavir in adolescents and young adults with human immunodeficiency virus infection. Antimicrob Agents Chemother 52: 631–637.
