Week 144, 328 patients (87%) were still undergoing
an intent-to-treat analysis, 87% of HBeAg negative
patients had sustained HBV DNA suppression < 400
copies/mL at Week 144.
was similar in patients who received tenofovir monotherapy
for the entire study and those who started on adefovir
and later switched to tenofovir (87% vs 88%, respectively).
an as-treated analysis, 99% of participants in the
ongoing tenofovir arm and 100% in the adefovir-to-tenofovir
arm achieved undetectable HBV viral load by Week 144.
patients with continued HBV viremia added emtricitabine
at or after Week 72, and all achieved undetectable
viral load by Week 144.
other participants still had viral load of 400 copies/mL
or more at week 144.
aminotransferase (ALT) levels remained normal through
Week 144 (overall mean 33 U/L).
participants experienced hepatitis B surface antigen
(HBsAg) loss by Week 144.
tenofovir was well-tolerated through Week 144.
drug-related serious adverse event (mild kidney impairment)
was reported in the ongoing tenofovir arm and none
in the adefovir-to-tenofovir arm.
rate of serious (grade 3-4) laboratory abnormalities
was similar in the ongoing tenofovir and adefovir-to-tenofovir
arms (14% vs 15%, respectively).
participants (1.3%) in the ongoing tenofovir arm discontinued
treatment due to adverse events (hepatocellular carcinoma,
dizziness/fatigue/lack of concentration, and septic
participants experienced a confirmed 0.5 mg/dL increase
in serum creatinine or a decrease in creatinine clearance
to less than 50 mL/min (indicators of kidney function
deaths occurred during the open-label phase, none
of them considered attributable to tenofovir (nasopharyngeal
cancer, metastatic liver cancer, and cervical cancer).
evidence of drug resistance mutations was observed
through 144 weeks.
Study 103 Results
Week 144, 214 patients (80%) were still undergoing
an intent-to-treat analysis, 71% of HBeAg positive
patients had sustained HBV DNA < 400 copies/mL
at Week 144.
efficacy was similar in patients who received ongoing
tenofovir and those who switched from adefovir to
tenofovir (72% vs 71%, respectively).
an as-treated analysis, 95% of patients in the ongoing
tenofovir arm and 91% in the adefovir-to-tenofovir
arm achieved undetectable HBV DNA by Week 144.
participants with confirmed viremia added emtricitabine
between 72 and 144 weeks, and 17 achieved undetectable
viral load by Week 144.
patients still had HBV viral load of 400 copies/mL
or more at Week 144.
of participants achieved HBeAg loss and 26% experienced
experienced HBsAg loss.
levels were near normal by week 144 (mean 39 U/L).
tenofovir was generally well-tolerated through Week
drug-related serious adverse events were reported
in the ongoing tenofovir arm (increased ALT and
facial spasm) and 2 in the adefovir-to-tenofovir
of patients in the ongoing tenofovir arm and 16%
in the adefovir-to-tenofovir arm experienced grade
3-4 laboratory abnormalities.
patient discontinued tenofovir due to a 0.5 mg/dL
increase in creatinine, and 2 participants in the
adefovir-to-tenofovir arm had confirmed 0.5 mg/dL
creatinine increases, but none experienced a decrease
in creatinine clearance to less than 50 mL/min.
drug resistance mutations were observed through
the 2 studies combined, continued follow-up did not
reveal any new or unexpected adverse events or tolerability
problems beyond those observed during the first 48 weeks
of treatment. The most common adverse event overall
was nausea, occurring in 9% of patients at Week 48.
Other adverse events reported by more than 5% of participants
included abdominal pain, diarrhea, headache, dizziness,
fatigue, sore throat, back pain, and skin rash.
was well tolerated and produced potent, continuous viral
suppression and no mutations associated with [tenofovir]
resistance were detected through 3 years of [tenofovir]
treatment," concluded the Study 102 investigators.
Study 103 team confirmed this conclusion, adding that
tenofovir produced "increasing HBeAg and HBsAg
loss through 3 years of treatment in HBeAg positive
development of resistance is a significant challenge
for practitioners treating patients with chronic hepatitis
B," said Study 102 principal investigator Patrick
Marcellin in a press release issued by Gilead. "The
robust and comprehensive resistance surveillance in
these studies provides important information for the
medical community and shows that Viread offers a high
barrier to resistance."
102 team: Hopital Beaujon, University of Paris, Clichy,
France; Hospital General Universitari Vall d'Hebron
and Ciberehd, Barcelona, Spain; University Hospital
St Ivan Rilsky, Sofia, Bulgaria; Papageorgiou Peripheral
General Hospital of Thessaloniki, Thessaloniki, Greece;
University of Manitoba, Winnipeg, Manitoba, Canada;
University Hospital Sveta Marina, Varna, Bulgaria; Medizinische
Universitatsklinik Eppendorf, Hamburg, Germany; Waikato
Hospital, Hamilton, New Zealand; San Jose Gastroenterology,
San Jose, CA; University of Uludag, Bursa, Turkey; University
of Toronto, Toronto, Ontario, Canada; Gilead Sciences,
103 team: University of Toronto, Toronto, Ontario, Canada;
Middlemore Hospital, Auckland, New Zealand; Erasmus
MC, University Medical Center, Rotterdam, Netherlands;
University of Calgary, Calgary, Alberta, Canada; Medical
University of Bialystok, Bialystok, Poland; Medical
School of Hannover, Hannover, Germany; Medical University,
Sofia, Bulgaria; Haydarpapa Numune Hospital, Istanbul,
Turkey; Virginia Commonwealth University, Richmond,
VA; Hopital Beaujon, University of Paris, Clichy, France;
Gilead Sciences, Durham, NC.
Years of Tenofovir Disoproxil Fumarate (TDF) Treatment
in HBeAg-Negative Patients with Chronic Hepatitis B
(Study 102); Preliminary Analysis
P Marcellin, M Buti, Z Krastev, and others. 60th Annual
Meeting of the American Association for the Study of
Liver Diseases (AASLD 2009). Boston. October 30-November
1, 2009. Abstract 481.
Heathcote, EJ Gane, RA De Man, and others. Three Years
of Tenofovir Disoproxil (TDF) Treatment in HBeAg-Positive
Patients (HBeAg+) with Chronic Hepatitis B (Study 103),
Preliminary Analysis. 60th Annual Meeting of the American
Association for the Study of Liver Diseases (AASLD 2009).
Boston. October 30-November 1, 2009. Abstract 483.
Announces Long-Term Data from Two Pivotal Phase III
Studies Evaluating Viread For Chronic Hepatitis B.
Press release . October 31, 2009.