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

Ying Cao, Yang Han, Jing Xie, Qu Cui, Lixia Zhang, Yijia Li, Yanling Li, Xiaojing Song, Ting Zhu, Taisheng Li, Ying Cao, Yang Han, Jing Xie, Qu Cui, Lixia Zhang, Yijia Li, Yanling Li, Xiaojing Song, Ting Zhu, Taisheng Li

Abstract

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/1.73 m², 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. 6.4 ml/min/1.73 m², 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.

Figures

Figure 1
Figure 1
Changes in median serum creatinine concentrations at 0, 4, 8, 12, 24, 36, and 48 weeks in TDF+PI/r and control groups.
Figure 2
Figure 2
Changes in median eGFR at 0, 4, 8, 12, 24, 36, and 48 weeks in TDF+PI/r and control groups.
Figure 3
Figure 3
Changes in median eGFR over time in the TDF+PI/r group, by eGFR normal (eGFR≥90 ml/min/1.73m2) and abnormal (90>eGFR≥50 ml/min/1.73m2) baselines.

References

    1. Izzedine H, Harris M, Perazella MA. The nephrotoxic effects of HAART. Nat Rev Nephrol. 2009;5:563–573. doi: 10.1038/nrneph.2009.142.
    1. De Clercq E. New developments in anti-HIV chemotherapy. Curr Med Chem. 2001;8:1543–1572. doi: 10.2174/0929867013371842.
    1. Department of Health and Human Services. Guidelines for the use of antiretroviral agents in HIV-1 infected adults and adolescents. 2011. 2012-01-14]. .
    1. European AIDS Clinical Society (EACS) Guidelines for the clinical management and treatment of HIV infected adults in Europe. 5-4. 2011. .
    1. 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.
    1. 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. doi: 10.1086/499048.
    1. 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. doi: 10.1016/j.jinf.2004.08.031.
    1. 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. doi: 10.1053/ajkd.2002.36924.
    1. 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. doi: 10.1097/00002030-200404300-00019.
    1. 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. doi: 10.1007/s00428-007-0418-3.
    1. Thompson M, Haubrich R, Margolis D, Schneider S, Schooley R, Pappa KJ, 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.
    1. Gallant JE, Moore RD. Renal function with use of a tenofovir-containing initial antiretroviral regimen. AIDS. 2009;24:1971–1975.
    1. 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. doi: 10.1086/428840.
    1. 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. doi: 10.1097/QAD.0b013e3283112b8e.
    1. 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. doi: 10.1097/QAD.0b013e32834957da.
    1. 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. doi: 10.7326/0003-4819-145-4-200608150-00004.
    1. Peters PJ, Moore DM, Mermin J. et al.Antiretroviral therapy improves renal function among HIV-infected Ugandans. Kidney Int. 2008;74(7):925–929. doi: 10.1038/ki.2008.305.
    1. 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. doi: 10.1097/QAD.0b013e3283313c91.
    1. 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.
    1. 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. doi: 10.1089/apc.2009.0326.
    1. 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. doi: 10.1086/524061.
    1. 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. doi: 10.1097/01.qai.0000242461.35768.45.
    1. 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. doi: 10.1038/sj.clpt.6100269.
    1. 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. doi: 10.1097/01.qai.0000243103.03265.2b.
    1. Gilead Sciences. Viread Medication Insert. . [Accessed 15 December 2011.
    1. Miller DS. Nucleoside phosphonate interactions with multiple organic anion transporters in renal proximal tubule. J Pharmacol Exp Ther. 2001;299:567–574.
    1. 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. doi: 10.1053/j.ajkd.2011.01.022.
    1. 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. doi: 10.1086/533468.
    1. 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. doi: 10.1097/QAD.0b013e328339fe53.
    1. 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. doi: 10.1111/j.1468-1293.2006.00349.x.
    1. 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. doi: 10.1086/430257.
    1. 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. doi: 10.1097/QAD.0b013e32834bba87.

Source: PubMed

Sponsorer og samarbejdspartnere

Medicinske tilstande

Narkotikainterventioner

3
Abonner