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Treatment-limiting renal tubulopathy in patients treated with tenofovir disoproxil fumarate.

Hamzah, L; Jose, S; Booth, JW; Hegazi, A; Rayment, M; Bailey, A; Williams, DI; Hendry, BM; Hay, P; Jones, R; et al. Hamzah, L; Jose, S; Booth, JW; Hegazi, A; Rayment, M; Bailey, A; Williams, DI; Hendry, BM; Hay, P; Jones, R; Levy, JB; Chadwick, DR; Johnson, M; Sabin, CA; Post, FA (2017) Treatment-limiting renal tubulopathy in patients treated with tenofovir disoproxil fumarate. J Infect, 74 (5). pp. 492-500. ISSN 1532-2742 https://doi.org/10.1016/j.jinf.2017.01.010
SGUL Authors: Hay, Phillip Edward

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Abstract

OBJECTIVES: Tenofovir disoproxil fumarate (TDF) is widely used in the treatment or prevention of HIV and hepatitis B infection. TDF may cause renal tubulopathy in a small proportion of recipients. We aimed to study the risk factors for developing severe renal tubulopathy. METHODS: We conducted an observational cohort study with retrospective identification of cases of treatment-limiting tubulopathy during TDF exposure. We used multivariate Poisson regression analysis to identify risk factors for tubulopathy, and mixed effects models to analyse adjusted estimated glomerular filtration rate (eGFR) slopes. RESULTS: Between October 2002 and June 2013, 60 (0.4%) of 15,983 patients who had received TDF developed tubulopathy after a median exposure of 44.1 (IQR 20.4, 64.4) months. Tubulopathy cases were predominantly male (92%), of white ethnicity (93%), and exposed to antiretroviral regimens that contained boosted protease inhibitors (PI, 90%). In multivariate analysis, age, ethnicity, CD4 cell count and use of didanosine or PI were significantly associated with tubulopathy. Tubulopathy cases experienced significantly greater eGFR decline while receiving TDF than the comparator group (-6.60 [-7.70, -5.50] vs. -0.34 [-0.43, -0.26] mL/min/1.73 m2/year, p < 0.0001). CONCLUSIONS: Older age, white ethnicity, immunodeficiency and co-administration of ddI and PI were risk factors for tubulopathy in patients who received TDF-containing antiretroviral therapy. The presence of rapid eGFR decline identified TDF recipients at increased risk of tubulopathy.

Item Type: Article
Additional Information: © 2017. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/
Keywords: Antiretroviral, Fanconi, HIV, Kidney, Renal, TDF, Tenofovir, Toxicity, Tubulopathy, Adult, Anti-HIV Agents, Female, Glomerular Filtration Rate, HIV Infections, Humans, Kidney Diseases, Male, Middle Aged, Tenofovir, HIV, Tubulopathy, Fanconi, Renal, Kidney, Antiretroviral, Toxicity, Tenofovir, TDF, Antiretroviral, Fanconi, HIV, Kidney, Renal, TDF, Tenofovir, Toxicity, Tubulopathy, Microbiology, 1103 Clinical Sciences
SGUL Research Institute / Research Centre: Academic Structure > Infection and Immunity Research Institute (INII)
Journal or Publication Title: J Infect
ISSN: 1532-2742
Language: eng
Dates:
DateEvent
May 2017Published
25 January 2017Published Online
17 January 2017Accepted
Publisher License: Creative Commons: Attribution-Noncommercial-No Derivative Works 4.0
Projects:
Project IDFunderFunder ID
MR/M004236/1Medical Research Councilhttp://dx.doi.org/10.13039/501100000265
DRF-2009-02-54National Institute for Health Researchhttp://dx.doi.org/10.13039/501100000272
G0800247Medical Research Councilhttp://dx.doi.org/10.13039/501100000265
G0900274Medical Research Councilhttp://dx.doi.org/10.13039/501100000265
PubMed ID: 28130143
Web of Science ID: WOS:000399488700008
Go to PubMed abstract
URI: http://openaccess.sgul.ac.uk/id/eprint/109891
Publisher's version: https://doi.org/10.1016/j.jinf.2017.01.010

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