Incomplete Reversibility of Estimated Glomerular Filtration Rate Decline Following Tenofovir Disoproxil Fumarate Exposure

• Published in: The Journal of infectious diseases Vol. 210; no. 3; pp. 363 - 373
• Main Authors: Jose, Sophie, Hamzah, Lisa, Campbell, Lucy J., Hill, Teresa, Fisher, Martin, Leen, Clifford, Gilson, Richard, Walsh, John, Nelson, Mark, Hay, Phillip, Johnson, Margaret, Chadwick, David, Nitsch, Dorothea, Jones, Rachael, Sabin, Caroline A., Post, Frank A.
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01.08.2014
• Subjects: Adenine - adverse effects; Adenine - analogs & derivatives; Adenine - therapeutic use; Adult; AIDS; Anti-HIV Agents - adverse effects; Anti-HIV Agents - therapeutic use; Antiretrovirals; Biological and medical sciences; Carts; Cohort Studies; Drug Administration Schedule; Female; Fundamental and applied biological sciences. Psychology; Funding; Glomerular filtration rate; Glomerular Filtration Rate - drug effects; Health care industry; HIV; HIV Infections - drug therapy; HIV/AIDS; Humans; Infectious diseases; Kidney Diseases - chemically induced; Major and Brief Reports; Male; Medical research; Medical sciences; Microbiology; Middle Aged; Organophosphonates - adverse effects; Organophosphonates - therapeutic use; Proportional Hazards Models; Renal function; Tenofovir; Viral Load; Purine nucleotide; Antiretroviral agent; Acyclic nucleotide; RNA-directed DNA polymerase; Enzyme; Transferases; Enzyme inhibitor; Organic phosphonate; Nucleotide analog; Infection; Tenofovir; Nucleotidyltransferases; Reverse transcriptase inhibitor; Nucleoside analog; Antiviral; eGFR; eGFR slopes; highly active antiretroviral therapy; kidney; renal function; tenofovir
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1093/infdis/jiu107

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 m²/year [95% confidence interval {CI}, -20.5 to -10.9] during the first 3 months and -3.1 mL/minute/1.73 m²/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 m²/year [95% CI, 8.9-16.1] during the first 3 months and 0.8 mL/minute/1.73 m²/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.