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Chapter 4.2
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release. Although we cannot rule out a possible effect of tenofovir on blocking infection
(η varying between 0 and 100%), the viral kinetic data for ten ofovir could be fi tted
assuming both effects (η = 1 and η = 0).
The HBV-DNA levels can fl uctuate even in untreated pa tients. However, pretreatment
levels of HBV-DNA in the patients in our study were similar to t = 0. This suggests that
the rapid decrease in HBV-DNA levels after t = 0 could be attributed to treatment with
tenofovir, and was not the consequence of a spontaneous decrease.
In our study, 4 weeks after addition of tenofovir to the treatment regimen, a mean log
HBV-DNA decline of 2.54 ± 0.91 (median 2.34; range: 1.33 4.02) could be observed.
This is comparable with the 2.42 log HBV-DNA decline found in a study with tenofovir
in fi ve HIV/HBV co infected resistant patients, 12 and is higher than the 0.9 log HBV-DNA
decline in a study performed in 12 HIV/ HBV co-infected patients who were treated with
tenofovir. 11
Taken together, the data which showed a mean log HBV-DNA decline of 4.95 ± 0.90 log
HBV-DNA (median 5.05; range: 3.64 5.94) after 24 weeks of tenofovir in our study and the
data which showed a mean log decline of 3.4 copies/ mL after 24 weeks treatment with
adefovir in lamivudine resistant HIV/HBV co-infected patients, 27 suggests that tenofovir
may have an important role to play in patients who experience breakthrough viraemia
on lamivudine therapy.
The second-phase decline in viral levels refl ects the death rate of productively infected
cells. The death of these cells is thought to require a host immune response. A possible
marker of the strength of host immune response is the level of ALT, which is an indicator
of the level of cell damage and death.
Previously, authors have observed a positive correlation between the decay rate of
infected cells and the pretreatment ALT level among chronic HBV patients who were
treated with lamivudine therapy. 25 Another study, which analysed the infl uence of lamivudine
dose and baseline ALT on the viral dynamics of the HBV, confi rmed that higher
baseline ALT levels were signifi cantly related to the slope of the second-phase of viral
decay. 28
Nevertheless, in another study, in which patients were treated with either lamivudine
monotherapy or with a combination of lamivudine and famciclovir, the investigators
found no association between the slope of the second-phase and baseline ALT. 29 This
is in agreement with our study, in which kinetic parameters λ1 , λ2 and e were not associated
with the pretreatment ALT levels. This discrepancy with some other studies may
be explained by the selection of patients in our study, which included patients with only
moderate elevation of ALT. We speculate that the ALT levels were too low to produce a
detectable association with the slope of viral decay.