nucleoside/nucleotide analog drugs are effective against HBV,
but the virus can develop drug resistance mutations that compromise
the efficacy long-term therapy. Experience with HIV indicates
that this is most likely to occur when these drugs are used as
A. Snow-Lampart and colleagues from Gilead Sciences conducted
population and clonal analyses of HBV polymerase from hepatitis
B "e" antigen (HBeAg) negative chronic hepatitis B patients
in the pivotal Study 102 and HBeAg positive participants in Study
103 who had persistent viremia (HBV DNA never fell below >400
copies/mL) or viral breakthrough (viral load 400 copies/mL after
suppression below this level) after up to 144 weeks on tenofovir.
The investigators looked at 641 total participants (333 from Study
102 and 225 from Study 103) who were still being followed at year
3. Starting at week 72, persistently viremic patients had the
option to add emtricitabine to tenofovir (the 2 drugs in the Truvada
combination pill). Among the 51 patients who were eligible
to add emtricitabine, 34 (67%) did so and 17 (33%) remained on
of 17 participants (71%) who remained on tenofovir alone
achieved HBV DNA < 400 copies/mL at week 144 or their
last visit, compared with 22 of 34 (65%) who added emtricitabine
(not a significant difference).
the 17 participants who remained viremic at their last visit
(5 on tenofovir monotherapy, 12 on tenofovir/emtricitabine),
5 qualified for clonal analysis due to persistent viremia,
1 of whom was non-adherent.
the remaining 4 patients, baseline viral load raged from
6.1 to 10.4 log and the median decline in HBV DNA was 6.1
log at week 144.
these 4 patients, clonal analysis revealed mutations in
HBV polymerase/reverse transcriptase (rt) at 19 distinct
positions, accounting for 3.6% to 9.1% of the total viral
a single conserved mutation (rtF183L) was present in clones
from more than 1 person.
the 12 other participants with HBV viremia at week 144 or
their last visit, 6 were non-adherent and 2 develop conserved
mutations (rtR192H and rtG152E).
these genotypic mutations, phenotypic testing found that
HBV from these patients remained sensitive to tenofovir
in vitro, and mutations were not associated with viral breakthrough.
Based on these findings, the investigators concluded, "Through
144 weeks of [tenofovir] therapy, no resistance mutations to tenofovir
have been identified among HBeAg negative and HBeAg positive patients
in two Phase 3 studies."
Among the 51 tenofovir-treated participants with HBV viremia at
week 72 or after, "addition of [emtricitabine] did not appear
to impact the subsequent decline in HBV DNA as compared to patients
who maintained [tenofovir] monotherapy," they continued.
Finally, they added, "Persistent viremia among adherent patients
was rare (4/641, 0.6%) and not associated with virologic resistance
to tenofovir as detected by population or clonal analyses."
Gilead Sciences, Inc, Durham, NC; Gilead Sciences, Inc, Foster
A Snow-Lampart, B Chappell, J Sorbel, and others. Evaluation
of potential virologic resistance in HBV polymerase among subjects
with persistent viremia following up to 144 weeks of therapy
with tenofovir DF. 45th Annual Meeting of the European Association
for the Study of the Liver (EASL 2010). Vienna, Austria. April
14-18, 2010. (Abstract).