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1844
Improved Renal Laboratory Parameters In CHB Patients
Treated With TAF Compared With Tenofovir Disoproxil
Fumarate (TDF)
Kosh Agarwal2, Norihiro Furusyo3, Kwan Soo Byun4, Jaeseok
Hwang5, John F. Flaherty1, Kyungpil Kim1, Anuj Gaggar1, Mani
Subramanian1, Maciej S. Jablkowski6, Alexey A. Yakovlev9, Huy
N. Trinh7, Maria Buti8; 1Gilead Sciences, Foster City CA, CA;
2Kings College Hospital NHS Trust, London, United Kingdom;
3Kyushu Medical Center, Fukuoka, Japan; 4Internal Medicine,
Korea University, Seoul, Korea (the Republic of); 5Keimyung University
Dongsan Medical Center, Daegu, Korea (the Republic of);
6Infectious and Liver Diseases, Oddziak Obserwacyjno-Zakazny,
Lodz, Poland; 7Silicon Valley Research Institute, San Jose, CA;
8Hospital Universitari Vall d’Hebron, Barcelona, Spain; 9Clinical
Infectious Diseases Hospital n.a. S.P.Botkin, St. Petersburg, Russian
Federation
Background: TDF treatment results in high rates of viral suppression
with no described resistance; however its use has
been associated with declines in eGFR over time. Phase 3
studies of TAF in CHB demonstrated lower declines in eGFR
compared to TDF over 48 weeks of treatment. Here, we further
characterize the clinical renal benefits of TAF compared to TDF.
Methods: In two identically-designed Phase 3 studies of TAF
(Study 110 in HBeAg positive and Study 108 in HBeAg negative
patients), patients were randomized 2:1 to TAF 25 mg QD
or TDF 300 mg QD, each with matching placebo, and treated
for 96 weeks. After Week 96, patients receive open label TAF
for 48 weeks. Renal parameters including eGFR calculated
by Cockcroft-Gault and CKD-EPI were evaluated throughout
the study period. Chronic kidney disease (CKD) staging was
categorized according to the NKF KDOQI guidelines (Stage
1: eGFR ≥ 90mL/min; Stage 2: eGFR 60-90 mL/min; Stage 3
eGFR 30-59 mL/min). Evaluated risk factors for kidney disease
included older age (age ≥ 50) and comorbidities of hypertension
(HTN), cardiovascular disease (CVD) and diabetes (DM).
Multivariate analysis was performed using backwards stepwise
approach. Results: Baseline demographics between TAF
and TDF groups in both studies were generally balanced for
risk factors for kidney disease. At week 48, patients treated
with TAF had smaller changes in creatinine (median change
0.01 mg/dL for TAF and 0.02 mg/dL for TDF; p=0.012) and
eGFRCG (median change -1.2 mL/min for TAF and -5.4 mL/min
for TDF; p<0.001) during 48 weeks of treatment. The number
of patients who had >25% eGFRCG reductions was also greater
in the TDF arm versus the TAF arm (14.5% vs 8.7%, p=0.002).
Using stages of CKD, a higher percentage of patients treated
with TDF had one or more stage worsening in renal function at
Week 48 (10.6% vs 6.7%; p=0.002; table). Among patients
at highest risk for kidney disease (older age and comorbidities
of HTN, CVD or DM), significantly more TDF-treated patients
had worsening of renal function compared to TAF-treated
patients. Multivariate analysis of worsening renal function by
CKD stage identified lower baseline eGFR, lower baseline
BMI, and Age ≥ 50 as independent predictors. Conclusions: In
patients with CHB, TAF therapy is associated with less effects
on renal parameters compared with TDF treatment. The benefits
of TAF may be particularly evident in patients at higher risk of
eGFR decline.
% Patients with Chronic Kidney Disease Stage Changes
HTN, hypertension; CVD, cardiovascular disease; DM, diabetes
Disclosures:
Kosh Agarwal - Advisory Committees or Review Panels: Gilead, BMS, Novartis,
Janssen, AbbVie; Consulting: MSD, Janssen, Achillion, Intercept; Grant/Research
Support: Roche, Gilead, BMS, Arbutus; Speaking and Teaching: Astellas, Gilead,
BMS, GSK
Kwan Soo Byun - Grant/Research Support: Gilead, BMS
John F. Flaherty - Employment: Gilead Sciences; Stock Shareholder: Gilead Sciences
Anuj Gaggar - Employment: Gilead Sciences, Inc.
Maciej S. Jablkowski - Advisory Committees or Review Panels: Gilead, Abbvie;
Consulting: BMS, Gilead, Roche, MSD; Speaking and Teaching: BMS, Roche,
MSD, Janssen-Cilag, Novartis
Huy N. Trinh - Grant/Research Support: Gilead, Intercept, Abbvie, merk; Speaking
and Teaching: Gilead; Stock Shareholder: Gilead
Maria Buti - Advisory Committees or Review Panels: Gilead, Janssen, MSD;
Grant/Research Support: Gilead, Janssen; Speaking and Teaching: Gilead,
Janssen, BMS
The following people have nothing to disclose: Norihiro Furusyo, Jaeseok
Hwang, Kyungpil Kim, Mani Subramanian, Alexey A. Yakovlev
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