Background: Cases of renal dysfunction have been reported in HIV-infected patients taking tenofovir (TDF), but few large studies have examined population-level changes in renal function associated with TDF use in patients in routine care. Methods: The authors analyzed data from participants in the HIV Outpatient Study (HOPS) who had normal baseline renal function and received >1 month of TDF-containing (n = 593) or TDF-sparing (n = 521) HAART after November 1, 2001. Results: Median baseline CrCl estimated by Cockcroft-Gault equation was 106 mL/min for TDF-exposed and 110 mL/min for TDF-unexposed patients (P = 0.06). In multivariable analyses, 1-year changes in CrCl (mL/min) from baseline were —5.7 among TDF-exposed and 2.6 among TDF-unexposed (P < 0.001). Incident renal disease was diagnosed in 7 TDF-exposed and 3 TDF-unexposed patients. Conclusions: In this large cohort of HIV-infected outpatients, use of TDF-containing HAART was associated with modest decreases in CrCl during the first year, but not with frequent, clinically significant renal toxicity.
Gallant JE, Deresinski S.Tenofovir disoproxil fumarate. Clin Infect Dis.2003;37:944-950.
2.
Panel on Clinical Practices for Treatment of HIV Infection convened by the Department of Health and Human Services.Guidelines for the use of antiretroviral agents in HIV-1—infected adults and adolescents . Available at: http://AIDSinfo.nih.gov. Accessed March 17, 2006.
3.
Kahn J., Lagakos S., Wulfsohn M., et al. Efficacy and safety of adefovir dipivoxil with antiretroviral therapy: a randomized controlled trial. JAMA.1999;282:2305-2312.
4.
Ho ES, Lin DC, Mendel DB, Cihlar T.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.
5.
Van Rompay KK , Brignolo LL, Meyer DJ, et al. Biological effects of short-term or prolonged administration of 9-[2-(phosphonomethoxy)propyl]adenine (tenofovir) to newborn and infant rhesus macaques. Antimicrob Agents Chemother.2004;48:1469-1487.
6.
Tarantal AF, Marthas ML, Shaw JP, Cundy K., Bischofberger N.Administration of 9-[2-(R)-(phosphonomethoxy)propyl]adenine (PMPA) to gravid and infant rhesus macaques (Macaca mulatta): safety and efficacy studies. J Acquir Immune Defic Syndr Hum Retrovirol. 1999;20:323-333.
7.
Schooley RT, Ruane P., Myers RA, et al. Tenofovir DF in antiretroviral-experienced patients: results from a 48-week, randomized, double-blind study. AIDS. 2002;16:1257-1263.
8.
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.
9.
Izzedine H., Hulot JS, Vittecoq D., 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. Nephrol Dial Transplant.2005;20:743-746.
10.
Gallant JE, Staszewski S., Pozniak AL, et al. Efficacy and safety of tenofovir DF vs stavudine in combination therapy in antiretroviral-naive patients: a 3-year randomized trial. JAMA.2004; 292:191-201.
11.
Gallant JE, DeJesus E., Arribas JR, et al. Tenofovir DF, emtricitabine, and efavirenz vs. zidovudine, lamivudine, and efavirenz for HIV. N Engl J Med.2006;354:251-260.
12.
Peyriere H. , Reynes J., Rouanet I., et al. Renal tubular dysfunction associated with tenofovir therapy: report of 7 cases. J Acquir Immune Defic Syndr. 2004;35:269-273.
13.
Izzedine H. , Isnard-Bagnis C., Hulot JS, et al. Renal safety of tenofovir in HIV treatment-experienced patients. AIDS. 2004;18:1074-1076.
14.
Zimmermann AE, Pizzoferrato T., Bedford J., et al. Tenofovir-associated acute and chronic kidney disease: a case of multiple drug interactions. Clin Infect Dis.2006;42:283-290.
15.
Antoniou T. , Raboud J., Chirhin S., et al. Incidence of and risk factors for tenofovir-induced nephrotoxicity: a retrospective cohort study. HIVMed.2005;6:284-290.
16.
Gallant JE, Parish MA, Keruly JC, Moore RDChanges in renal function associated with tenofovir disoproxil fumarate treatment, compared with nucleoside reverse-transcriptase inhibitor treatment . Clin Infect Dis.2005; 40:1194-1198.
17.
Winston A., Amin J., Mallon PW, et al. Minor changes in calculated creatinine clearance and anion-gap are associated with Tenofovir DF containing highly active antiretroviral therapy . HIV Med.2006;7:105-111.
18.
Gallant JE, Parish MA, Keruly JC, Moore RDReply to Gupta. Clin Infect Dis.2005 ;41:571-572.
19.
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.
20.
Cockcroft DW , Gault MHPrediction of creatinine clearance from serum creatinine. Nephron.1976;16:31-41.
21.
K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Am J Kidney Dis.2002;39:S1-S266.
22.
Division of AIDS table for grading the severity of adult and pediatric adverse events, December 2004. Available at: http://rcc.tech-res-intl.com/tox_tables.htm. Accessed March 17, 2006.
23.
Jones R., Stebbing J., Nelson M., et al. renal dysfunction with tenofovir disoproxil fumarate-containing highly active antiretroviral therapy regimens is not observed more frequently: a cohort and case-control study. J Acquir Immune Defic Syndr.2004;37:1489-1495.
24.
Moreno S., Domingo P., Palacios R., et al. 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. J Acquir Immune Defic Syndr . 2006;42:385-387.
25.
Gupta SK, Eustace JA, Winston JA, et al. 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.2005; 40:1559-1585.
