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Incomplete reversibility of estimated glomerular filtration rate decline following tenofovir disoproxil fumarate exposure.

Jose, S; Hamzah, L; Campbell, LJ; Hill, T; Fisher, M; Leen, C; Gilson, R; Walsh, J; Nelson, M; Hay, P; et al. Jose, S; Hamzah, L; Campbell, LJ; Hill, T; Fisher, M; Leen, C; Gilson, R; Walsh, J; Nelson, M; Hay, P; Johnson, M; Chadwick, D; Nitsch, D; Jones, R; Sabin, CA; Post, FA; UK Collaborative HIV Cohort Study Steering Committee (2014) Incomplete reversibility of estimated glomerular filtration rate decline following tenofovir disoproxil fumarate exposure. Journal of Infectious Diseases, 210 (3). pp. 363-373. ISSN 1537-6613 https://doi.org/10.1093/infdis/jiu107
SGUL Authors: Hay, Phillip Edward

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Abstract

BACKGROUND: Tenofovir disoproxil fumarate (TDF) has been linked to renal impairment, but the extent to which this impairment is reversible is unclear. We aimed to investigate the reversibility of renal decline during TDF therapy. METHODS: Cox proportional hazards models assessed factors associated with discontinuing TDF in those with an exposure duration of >6 months. In those who discontinued TDF therapy, linear piecewise regression models estimated glomerular filtration rate (eGFR) slopes before initiation of, during, and after discontinuation of TDF therapy. Factors associated with not achieving eGFR recovery 6 months after discontinuing TDF were assessed using multivariable logistic regression. RESULTS: We observed declines in the eGFR during TDF exposure (mean slopes, -15.7 mL/minute/1.73 m(2)/year [95% confidence interval {CI}, -20.5 to -10.9] during the first 3 months and -3.1 mL/minute/1.73 m(2)/year [95% CI, -4.6 to -1.7] thereafter) and evidence of eGFR increases following discontinuation of TDF therapy (mean slopes, 12.5 mL/minute/1.73 m(2)/year [95% CI, 8.9-16.1] during the first 3 months and 0.8 mL/minute/1.73 m(2)/year [95% CI,.1-1.5] thereafter). Following TDF discontinuation, 38.6% of patients with a decline in the eGFR did not experience recovery. A higher eGFR at baseline, a lower eGFR after discontinuation of TDF therapy, and more-prolonged exposure to TDF were associated with an increased risk of incomplete recovery 6 months after discontinuation of TDF therapy. CONCLUSIONS: This study shows that a decline in the eGFR during TDF therapy was not fully reversible in one third of patients and suggests that prolonged TDF exposure at a low eGFR should be avoided.

Item Type: Article
Additional Information: © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
Keywords: eGFR, eGFR slopes, highly active antiretroviral therapy, kidney, renal function, tenofovir, Adenine, Adult, Anti-HIV Agents, Cohort Studies, Drug Administration Schedule, Female, Glomerular Filtration Rate, HIV Infections, Humans, Kidney Diseases, Male, Middle Aged, Organophosphonates, Proportional Hazards Models, Viral Load, Science & Technology, Life Sciences & Biomedicine, Immunology, Infectious Diseases, Microbiology, CHRONIC KIDNEY-DISEASE, HIV-INFECTED PATIENTS, INITIATING ANTIRETROVIRAL THERAPY, RENAL-FUNCTION, NAIVE PATIENTS, TUBULAR DYSFUNCTION, POSITIVE PATIENTS, RISK-FACTORS, CYSTATIN-C, TOXICITY, 11 Medical And Health Sciences, 06 Biological Sciences
SGUL Research Institute / Research Centre: Academic Structure > Infection and Immunity Research Institute (INII)
Journal or Publication Title: Journal of Infectious Diseases
ISSN: 1537-6613
Language: eng
Dates:
DateEvent
1 August 2014Published
PubMed ID: 24585896
Web of Science ID: WOS:000340242900005
Go to PubMed abstract
URI: https://openaccess.sgul.ac.uk/id/eprint/107268
Publisher's version: https://doi.org/10.1093/infdis/jiu107

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