SAFE AND POTENT SUPPRESSION OF HEPATITIS B VIRUS (HBV) WITH L-DEOXYTHYMIDINE (LDT): RESULTS OF A DOSE-ESCALATION TRIAL
- NATAP - www.natap.org
Nov 9-13, Dallas
Reported by Jules Levin
Abstract 597. SAFE AND POTENT SUPPRESSION OF HEPATITIS
B VIRUS (HBV) WITH L-DEOXYTHYMIDINE (LDT): RESULTS OF
A DOSE-ESCALATION TRIAL
Ching-Lung Lai, Univ of Hong Kong, Pok Fu Lam Hong
Kong; Maureen W
Deborah M Pow, Nathaniel A Brown, Novirio
MA; Yin-Mei Lee, National Univ Hosp, Singapore
of Hong Kong, Pok Fu Lam Hong Kong; Seng Gee Lim,
National Univ Hosp,
Background: Therapy for chronic hepatitis B (CHB) is
suboptimal due to
frequent non-response to interferon and resistance
with lamivudine. LdT
potent anti-HBV activity in vitro and in the woodchuck
animal model and
potentially attractive safety profile (Bryant et al.,
AAC Jan 2001).
Methods: The antiviral activity of LdT in adults with
CHB is being
investigated in a dose-escalation trial, assessing 25,
50, 100, 200 and
mg once a day for 4 weeks with 12 weeks follow-up.
Serum HBV DNA levels
monitored weekly by a quantitative PCR method (COBAS
assay, Roche Molecular Systems).
Results: Four dosing cohorts (25, 50, 100, and 200
total patients, have completed treatment to date, with
the 400 mg/day
presently ongoing. Over 4 weeks of treatment, mean
HBV DNA levels have been 2.4�0.3 log10, 2.7�0.2 log10,
2.9�0.2 log10 for the 25, 50, 100 and 200 mg/day
all LdT doses have been highly active, producing >99%
viral load within 4 weeks in most patients. In the
ongoing 400 mg/day
HBV DNA reductions as high as 3.6 log10 have been
observed by week 4.
Analysis of serum HBV DNA reductions after Week 1
HBV clearance is dose-proportional, and post-treatment
return of HBV
slower in the higher dose groups, consistent with a
HBV-infected hepatocytes. Pharmacokinetic data
indicate that daily LdT
dose-proportional, so higher LdT doses will be tested
even greater HBV suppression can be achieved early
Conclusions: LdT appears promising as a potent and
safe new HBV
with marked anti-HBV activity within 4 weeks and a
suppression with higher and/or longer dosing. No
toxicities have been identified to date.
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