Impact of a tenofovir disoproxil fumarate plus ritonavir-boosted protease inhibitor-based regimen on renal function in HIV-infected individuals: a prospective, multicenter study

BMC Infectious Diseases

Taisheng Li¹  Ting Zhu¹  Xiaojing Song¹  Yanling Li¹  Yijia Li¹  Lixia Zhang¹  Qu Cui¹  Jing Xie¹  Yang Han¹  Ying Cao¹ 

[1] Department of Infection, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China

关键词: Protease Inhibitor;    Tenofovir;    Renal Function;    HIV;    Antiretroviral Therapy;   

Others  :  1147272
DOI  :  10.1186/1471-2334-13-301

 received in 2012-10-22, accepted in 2013-06-27,  发布年份 2013

【 摘 要 】

Background

The aim of this study was to investigate the impact of a tenofovir disoproxil fumarate (TDF) plus ritonavir-boosted protease inhibitor (PI/r) regimen on renal function in Chinese HIV-infected patients.

Methods

Seventy-five HIV-1 infected patients failing first-line antiretroviral therapy (ART) comprised the TDF+PI/r group. Seventy-five HIV-1 infected patients matched for gender, age, and renal function made up the control. All subjects completed follow-up visits over 48 weeks. CD4 cell count, plasma HIV-1 viral load, and urine protein level were assessed at the trial start (baseline, week 0) and at week 48. The serum creatinine and estimated glomerular filtration rate (eGFR) were monitored at each follow-up point. Change in eGFR from baseline to week 48 was also compared.

Results

Compared to control, the TDF+PI/r group exhibited higher levels of serum creatinine (79 vs. 69.7 μmol/L, P<0.001) and a lower rate of eGFR (93.0 vs. 101.6 ml/min/1.73m², P=0.009) at the end of week 48. Patients treated with TDF+PI/r showed greater decline in eGFR than control (−8.8 vs. 6.4ml/min/1.73m², P<0.001). Compared to baseline renal function of the control group, the TDF+PI/r group exhibited a greater median decline in eGFR at the end of week 48 (P<0.001).

Conclusions

We found that a TDF+PI/r based ART regimen resulted in greater renal function decline over 48 weeks. Therefore, renal function should be monitored especially when TDF is used in combination with PI/r.

Trial registration

ClinicalTrials.gov identifier: NCT00872417

【 授权许可】

   
2013 Cao et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 2.

Figure 3.

【 参考文献 】

• [1]Izzedine H, Harris M, Perazella MA: The nephrotoxic effects of HAART. Nat Rev Nephrol 2009, 5:563-573.
• [2]De Clercq E: New developments in anti-HIV chemotherapy. Curr Med Chem 2001, 8:1543-1572.
• [3]Department of Health and Human Services. Guidelines for the use of antiretroviral agents in HIV-1 infected adults and adolescents. 2011. 2012-01-14]. http://www.aidsinfo.nih.gov/contentfiles/lvguidelines/adultandadolescentgl.pdf webcite
• [4]European AIDS Clinical Society (EACS): Guidelines for the clinical management and treatment of HIV infected adults in Europe. 5-4 edition. 2011. http://www.europeanaidsclinicalsociety.org/Guidelines/G2.htm webcite
• [5]Cihlar T, Lin DC, Pritchard JB, Fuller MD, Mendel DB, Sweet DH: The antiviral nucleotide analogs cidofovir and adefovir are novel substrates for human and rat renal organic anion transporter 1. Mol Pharmacol 1999, 56:570-580.
• [6]Zimmermann AE, Pizzoferrato T, Bedford J, Morris A, Hoffman R, Braden G: Tenofovir-associated acute and chronic kidney disease: a case of multiple drug interactions. Clin Infect Dis 2006, 42:283-290.
• [7]Malik A, Abraham P, Malik N: Acute renal failure and Fanconi syndrome in an AIDS patient on tenofovir treatment: case report and review of literature. J Infect 2005, 51:E61-E65.
• [8]Verhelst D, Monge M, Meynard JL, Fouqueray B, Mouquenot B, Girard PM, et al.: Fanconi syndrome and renal failure induced by tenofovir: a first case report. Am J Kidney Dis 2002, 40:1331-1333.
• [9]Izzedine H, Isnard-Bagnis C, Hulot JS, Vittecoq D, Cheng A, Jais CK, et al.: Renal safety of tenofovir in HIV treatment experienced patients. AIDS 2004, 18:1074-1076.
• [10]Schmid S, Opravil M, Moddel M, Huber M, Pfammatter R, Keusch G, et al.: Acute interstitial nephritis of HIV-positive patients under atazanavir and tenofovir therapy in a retro-spective analysis of kidney biopsies. Virchows Arch 2007, 450:665-670.
• [11]Thompson M, Haubrich R, Margolis D, Schneider S, Schooley R, Pappa KJ, et al.: Differences in calculated glomerular filtration rates in efavirenz- or tenofovir-treated adults in ESS40006. Denver: Proceedings of the Thirteenth Conference on Retroviruses and Opportunistic Infections; 2006. Abstract no. 777
• [12]Gallant JE, Moore RD: Renal function with use of a tenofovir-containing initial antiretroviral regimen. AIDS 2009, 24:1971-1975.
• [13]Gallant JE, Parich MA, Keruly JC, Moore RD: Changes in renal function associated with Tenofovir Disoproxil Fumarate treatment, compared with nucleoside reverse-transcriptase inhibitor treatment. Clin Infect Dis 2005, 40:1194-1198.
• [14]Gallant JE, Winston JA, DeJesus E, Pozniak AL, Chen SS, Cheng AK, et al.: The 3-year renal safety of a tenofovir disoproxil fumarate vs a thymidine analogue-containing regimen in antiretroviral-naive patients. AIDS 2008, 22:2155-2163.
• [15]Brennana A, Evans D, Maskew M, Naicker S, Ive P, Sanne I, et al.: Relationship between renal dysfunction, nephrotoxicity and death among HIV adults on tenofovir. AIDS 2011, 25:1603-1609.
• [16]Levey AS, Coresh J, Greene T, 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, 145:247-254.
• [17]Peters PJ, Moore DM, Mermin J, et al.: Antiretroviral therapy improves renal function among HIV-infected Ugandans. Kidney Int 2008, 74(7):925-929.
• [18]Choi AI, Shlipak MG, Hunt PW, Martin JN, Deeks SG: HIV-infected persons continue to lose kidney function despite successful antiretroviral therapy. AIDS 2009, 23(16):2143-2149.
• [19]El-Sadr WM, Lundgren JD, Neaton JD, et al.: CD4+ count guided interruption of antiretroviral treatment. N Engl J Med 2006, 355(22):2283-2296.
• [20]Crum-Cianflone N, Ganesan A, Teneza-Mora N, Riddle M, Medina S, Barahona I, Brodine S: Prevalence and factors associated with renal dysfunction among HIV-infected patients. AIDS Patient Care STDS 2010, 24(6):353-60.
• [21]Goicoechea M, Liu S, Best B, Sun S, Jain S, Kemper C, et al.: Greater tenofovir-associated renal function decline with protease inhibitor-based versus nonnucleoside reverse-transcrip-tase inhibitor-based therapy. J Infect Dis 2008, 197:102-108.
• [22]Buchacz K, et al.: Renal function in patients receiving tenofovir with ritonavir/lopinavir or ritonavir/atazanavir in the HIV Outpatient Study (HOPS) cohort. J Acquir Immune Defic Syndr 2006, 43:626-628.
• [23]Kiser JJ, Carten ML, Aquilante CL, et al.: The effect of lopinavir/ritonavir on the renal clearance of tenofovir in HIV-infected patients. Clin Pharmacol Ther 2008, 83:265-272.
• [24]Kearney BP, Mathias A, Mittan A, Sayre J, Ebrahimi R, Cheng AK: Pharmacokinetics and safety of tenofovir disoproxil fuma-rate on coadministration with lopinavir/ritonavir. J Acquir Immune Defic Syndr 2006, 43:278-283.
• [25]Gilead Sciences: Viread Medication Insert. http://www.gilead.com/~/media/Files/pdfs/medicines/hiv/viread/viread_pi.pdf webcite. [Accessed 15 December 2011
• [26]Miller DS: Nucleoside phosphonate interactions with multiple organic anion transporters in renal proximal tubule. J Pharmacol Exp Ther 2001, 299:567-574.
• [27]Hall AM, Hendry BM, Nitsch D, Connolly JO: Tenofovir-associated kidney toxicity in HIV-infected patients: a review of theevidence. Am J Kidney Dis 2011, 57:773-780.
• [28]Reid A, Stöhr W, Walker AS, Williams IG, Kityo C, Hughes P, Kambugu A, Gilks CF, Mugyenyi P, Munderi P, Hakim J, Gibb DM: Development of Antiretroviral Therapy Trial. Severe renal dysfunction and risk factors associated with renal impairment in HIV-infected adults in Africa initiating antiretroviral therapy. Clin Infect Dis 2008, 46(8):1271-1281.
• [29]Mocroft A, Kirk O, Reiss P, De Wit S, Sedlacek D, Beniowski M, Gatell J, Phillips AN, Ledergerber B, Lundgren JD, EuroSIDA Study Group: Estimated glomerular filtration rate, chronic kidney disease and antiretroviral drug use in HIV-positive patients. AIDS 2010, 24(11):1667-78.
• [30]Winston A, Amin J, Mallon P, et al.: Minor changes in calculated creatinine clearance and anion-gap are asso-ciated with tenofovir disoproxil fumarate-containing highly active antiretroviral therapy. HIV Med 2006, 7:105-111.
• [31]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.
• [32]Vrouenraets SM, Fux CA, Wit FW, et al.: Persistent decline in estimated but not measured glomerular filtration rate on tenofovir may reflect tubular rather than glomerular toxicity. AIDS 2011, 25:2149-2155.