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

TY - JOUR

T1 - Treatment-limiting renal tubulopathy in patients treated with tenofovir disoproxil fumarate

AU - Hamzah, L.

AU - Jose, S.

AU - Booth, J. W.

AU - Hegazi, A.

AU - Rayment, M.

AU - Bailey, A.

AU - Williams, D. I.

AU - Hendry, B. M.

AU - Hay, P.

AU - Jones, R.

AU - Levy, J. B.

AU - Chadwick, D. R.

AU - Johnson, M.

AU - Sabin, C. A.

AU - Post, F. A.

PY - 2017/1/25

Y1 - 2017/1/25

N2 - 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.

AB - 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.

KW - Antiretroviral

KW - Fanconi

KW - HIV

KW - Kidney

KW - Renal

KW - TDF

KW - Tenofovir

KW - Toxicity

KW - Tubulopathy

UR - http://www.scopus.com/inward/record.url?scp=85011965308&partnerID=8YFLogxK

U2 - 10.1016/j.jinf.2017.01.010

DO - 10.1016/j.jinf.2017.01.010

M3 - Article

SN - 0163-4453

JO - The Journal of infection

JF - The Journal of infection

ER -