therapy is also complicated by development of Tenofovir
resistance, with resistance rates up to 21.6% after
Approved by the FDA in 2008, tenofovir is the
2 years of therapy among HBeAg-positive pa-
tients.26
Similar to the interferon treatment index, com-
most recent oral nucleotide analog introduced
for the treatment of CHB. Tenofovir has replaced
adefovir in clinical practice due to its superior ef-
prehensive analysis of patients undergoing therapy ficacy profile and low reported rates of resistance.
with telbivudine has determined certain baseline Two double-blind randomized phase III trials com-
pretreatment characteristics to help predict out-
pared 48 weeks of tenofovir therapy with adefovir.
comes.50 Among HBeAg-positive patients, serum Patients among the tenofovir group demonstrated
HBV DNA less than 9log10 copies/mL or ALT great-
er than 2 times the ULN at baseline along with un-
higher rates of viral suppression (76% versus
13%), normalization of serum ALT (68% versus
detectable HBV DNA at 24 weeks were the stron-
54%), histologic improvement (67% versus 12%),
gest predictors of a favorable treatment response. and HBsAg loss ( 3.2% versus 0%).52 Durability of
Among HBeAg-negative patients, baseline HBV treatment response was also superior to adefovir,
DNA less than 7log10 copies/mL and undetectable
HBV DNA at 24 weeks were predictors of favorable
with sustained viral suppression among 99% to
100% of patients after 4 years of therapy.53,54 Fur-
treatment response. Adhering to these parameters thermore, HBeAg loss was reported among 41% of
for selecting ideal telbivudine treatment candidates patients. Patients with HBV genotype A or D, pre-
is associated with significantly lower rates of resis-
tance.
treatment HBV DNA greater than 9log10 copies/mL,
and baseline histologic activity index (Knodell
One additional advantage of telbivudine com-
score) greater than 9 had higher likelihood of
pared with other nucleoside regimens is its more achieving HBsAg loss.54
favorable pregnancy category B safety rating. One
In addition to the superior efficacy in achieving
large study in China included 229 HBeAg-positive viral suppression, another major advantage of te-
mothers, comparing 135 women who were started nofovir is the low rate of resistance. Recent 5-year
on telbivudine during weeks 22–32 of gesta-
data presented at the AASLD annual scientific
tion and continued through 4 weeks postpartum, meeting reported no evidence of resistance after
and 94 controls who did not receive any antiviral up to 5 years of therapy.55
therapy.51 All infants received hepatitis B immune
Like telbivudine, tenofovir also holds a pregnancy
globulin (HBIG) within 12 hours postpartum and category B safety rating, and many of the studies
HBV vaccinations at 0, 1-, and 6-month intervals. evaluating its safety profile include both HIV and HBV
Mothers in the telbivudine treatment arm had patient cohorts. A recent large study utilizing data
higher rates of undetectable HBV DNA at time of from the Antiretroviral Pregnancy Registry (APR)
delivery (33% versus 0%) and higher rates of ALT included over 13,000 patients that were treated with
normalization (83% versus 57%). Furthermore, antiviral therapy during pregnancy. The overall prev-
there were no significant differences in the occur-
alence of birth defects among those treated with an-
rence of adverse events between the telbivudine tiviral therapy was no different from the rate among
group and the control group among both mothers population-based controls ( 2.8% versus 2.7%). The
and infants.
prevalence of birth defects among patients treated
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