Telbivudine monotherapy for HIV-HBV coinfected patients: an open explorative study.

Because HIV infection can accelerate progression of HBV-related liver disease,
treatment of chronic hepatitis B is generally recommended for most HIV-infected
persons with active HBV infection (e.g., elevated serum ALT level and HBV DNA
>10,000 IU/mL). However, the best strategy for management of HBV infection has
not been fully defined. Among patients with chronic HBV infection with no
current indication for HIV treatment (e.g., CD4 cell count >350 cells/mm3),
some experts recommend avoiding drugs active against HIV (e.g., emtricitabine,
lamivudine, entecavir and tenofovir) and suggest using the use of adefovir,
telbivudine and/or peginterferon. However, other experts recommend the
institution of a fully suppressive antiretroviral regimen that includes the use
of two agents active against HBV. This recommendation is based on the rationale
that control of HIV infection may represent an important step in preventing
HBV-related liver disease.
Therapy for HIV/HBV-coinfected patients for whom HIV treatment is indicated is
less controversial; most experts recommend the use of an antiretroviral regimen
that includes the use of two agents that are active against HBV (e.g.,
tenofovir plus emtricitabine or lamivudine).
Adefovir is a prodrug of tenofovir and although it has a high genetic barrier
against resistance in HBV in acts slowly and after 24 weeks monotherapy in HBV
monoinfected patients only 12-31 % reached an undetectable HBV load (1, 3).
Moreover, given the activity of tenofovir against HIV adefovir harbors the
possibility of inducing resistance (K65R mutation) in HIV. Therefore, it is not
a very appealing drug for treatment of HBV/HIV coinfected patients. Pegylated
interferon would be a possibility, especially in patients coinfected with HBV
genotype A. However, given the serious adverse events and the fact that a
considerable number of patients will develop lymfocytopenia, with a drop in the
already lowered CD4+ cells counts, many patients refuse therapy with
peg-interferon.
Telbivudine (β-L-2'-deoxythymidine) is an orally bioavailable L-nucleoside with
potent and specific anti-HBV activity. In preclinical toxicologic testing,
telbivudine had no mutagenic or carcinogenic effects and no appreciable
embryonic or fetal toxic effects * findings that are particularly relevant for
men and women in their reproductive years. In initial clinical trials,
treatment with telbivudine led to reductions in serum HBV DNA levels that were
greater than those observed with lamivudine, and resistance to telbivudine
developed less frequently than did resistance to lamivudine. Moreover, in a
recent study it was shown that among patients with HBeAg-positive chronic
hepatitis B, the rates of therapeutic and histologic response at 1 year were
significantly higher in patients treated with telbivudine than in patients
treated with lamivudine. In both the HBeAg-negative and the HBeAg-positive
groups, telbivudine demonstrated greater HBV DNA suppression with less
resistance than did lamivudine. At 24 wks 45% of HBeAg-positive patients had an
undetectable viral load, while Hbe-Ag-negative patients had an even higher rate
of undetectability (80%) (2, 3).
In another study in monoinfected HbeAg-positive patients Telbivudine
demonstrated greater and more consistent HBV DNA suppression than adefovir
after 24 weeks of treatment. After 52 weeks, HBV DNA suppression was greater in
patients who had received continuous telbivudine or were switched to
telbivudine after 24 weeks than in those who received continuous adefovir.
Moreover, at week 24 39% of patients had an undetectable viral load compared to
only 12 % of patients treated with adefovir. Telbivudine has no known activity
against HIV and therefore we propose an explorative study in HIV/HBV coinfected
patients not needing treatment of their HIV-infection with HAART.

Monitoring of resitance development in HIV

Open explorative study

Extra blood samples in total 100 ml in 48 weeks