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TITLE: Seven Years of Treatment with Tenofovir DF for Chronic Hepatitis B Virus Infection is Safe and Well Tolerated and Associated with Sustained Virological, Biochemical and Serological Responses with no Detectable Resistance
AUTHORS (FIRST NAME, LAST NAME): Patrick Marcellin1, Edward J. Gane2, Naoky Tsai3, Robert Flisiak4, Joerg Petersen5, Selim Gurel6, Iskren A. Kotzev7, John F. Flaherty8, Phillip Dinh8, Anuj Gaggar8, Kathryn M. Kitrinos8, Mani Subramanian8, John G. McHutchison8, Jacob George9, Maria Buti10
Institutional Author(s):
INSTITUTIONS (ALL): 1. Hopital Beaujon, Clichy, France.
2. Auckland City Hospital, Auckland, New Zealand.
3. University of Hawaii at Manoa, Honolulu, HI, United States.
4. Medical University of Bialystok, Bialystok, Poland.
5. Asklepios Klinik St. George, University of Hamburg, Hamburg, Germany.
6. Uludag Universitesi Tip Fakultesi, Bursa, Gorukle, Turkey.
7. University Hospital Sveta Marina, Varna, Bulgaria.
8. Gilead Sciences, Foster City, CA, United States.
9. Storr Liver Unit, Westmead Hospital, Sydney, NSW, Australia.
10. Hospital General Universitari Vall d’Hebron and Ciberehd, , Barcelona, Spain.
ABSTRACT BODY: Background:
We previously reported that 5 years of tenofovir DF (TDF) therapy in treatment naïve patients results in sustained viral suppression with no development of resistance and was associated with either the halting or regression of fibrosis in 96%, and reversal of cirrhosis in 74% of previously cirrhotic patients. Here we present 7 year results from these two ongoing 8 year studies (Studies 102 and 103).
Methods:
After 48 weeks of double-blind comparison of TDF to adefovir dipivoxil, all patients undergoing liver biopsy were eligible to continue open-label TDF. Patients were assessed every 3 months for safety and efficacy with annual resistance surveillance. Annual assessments of bone mineral density (BMD) by DXA were added to both studies starting at year 4.
Results:
In a total 641 patients who were initially randomized and treated, 585 (93%) entered the TDF extension phase at Year 1, and at Year 7, 437 (68%) remain on study. Efficacy results at Year 7 are shown in the table. Overall (both studies combined), TDF was well tolerated over the 7 year evaluation period. Less than 2.5% of patients discontinued TDF due to an adverse event, and ≤ 1.7% experienced a confirmed renal event (≥0.5 mg/dL increase in serum creatinine from baseline, or phosphorus <2 mg/dL, or CrCL <50 mL/min). BMD assessments (lumbar spine and hip T scores) were stable over 3 years of evaluation. No resistance to TDF has been detected through Year 7.
Conclusions:
In these two trials, TDF remains safe and effective over a 7 year treatment period with no detectable resistance to TDF; a relatively low rate of renal events and no evidence of clinically relevant bone loss were also observed.
HBeAg- Patients(Study 102)N=375 HBeAg+ Patients(Study 103)N=266
HBV DNA <400 copies/mL (mITT)a 77% (269/348) 60% (149/247)
HBV DNA <400 copies/mLb 99% (271/273) 99% (159/160)
ALT Normalizationb 84% (213/255) 74% (115/155)
HBeAg lossb - 54% (84/154)
HBeAg seroconversionb - 40% (61/154)
HBsAg loss (KM%)c -d 12% (n=26)
HBsAg seroconversion (KM%)c -d 10% (n=21)
aMissing-failure (LTE-TDF analysis set);bMissing=excluded (On treatment analysis set); cKaplan-Meier %; dOne patients experienced HBsAg loss and seroconversion at Week 240
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