Study Shows Hepatitis B Drug Entecavir (Baraclude) -- But Not Telbivudine (Tyzeka)
-- Has Activity against Multiple Strains of HIV
antiretroviral agents -- including tenofovir
(Viread), lamivudine (3TC, Epivir),
and emtricitabine (Emtriva) --
are active against both HIV and hepatitis
B virus (HBV), and therefore are well-suited for treating HIV-HBV
coinfected patients who require treatment for both diseases.
is more complex for coinfected people who need treatment for hepatitis B but do
not yet require HIV therapy based on symptoms or CD4 cell count.
important to avoid using a dually active agent on its own to treat HBV in coinfected
patients who are not on HAART, since the drug would act as monotherapy against
HIV and could spur the emergence of drug resistance. For this reason, current
U.S. antiretroviral treatment guidelines
recommend that all HIV-HBV coinfected patients who require hepatitis B treatment
-- regardless of CD4 cell count -- should use a combination antiretroviral regimen
that includes 2 agents that also work against HBV.
Earlier guidelines advised
that coinfected patients who did not yet need HIV therapy based on their CD4 count
could be treated for hepatitis B using agents without anti-HIV activity. Entecavir
(Baraclude) was thought to be such a drug, but at the 2007 Conference on Retroviruses
and Opportunistic Infections (CROI 2007) researchers presented evidence indicating
did have low-level activity against HIV and could select for resistant virus.
That left few agents active against HBV but not HIV. Telbivudine
(Tyzeka) may be one such drug, according to data presented by C. Avila and
colleagues from Novartis at the 44th Annual Meeting of
the European Association for the Study of the Liver (EASL 2009) last month
In a laboratory study, the investigators assessed 8 different
wild-type (non-mutated) clinical isolates of HIV, representing different geographic
locations and viral subtypes, for susceptibility to telbivudine and entecavir.
They also tested the susceptibility of 2 multi-drug resistant HIV isolates. Anti-HIV
activity was measured 48 hours after infection using the Monogram PhenoSense assay,
a sensitive and robust HIV phenotypic resistance test.
Telbivudine did not exhibit in vitro activity against any of the selected HIV
clinical isolates (50% inhibitory concentration [IC50] values > 600 µM).
In contrast, entecavir exhibited antiviral activity against most of the HIV clinical
isolates, at IC50 values ranging from 7.62 to 15.09 µM.
The IC50 of entecavir increased more than 8-fold in HIV isolates harboring the
in vitro study confirmed entecavir activity against HIV," the researchers
concluded. "In contrast telbivudine showed no antiviral effect against a
broad range of wild-type and multidrug resistant HIV isolates at IC50 values >
600 µM, which is well above physiologically relevant concentrations"
that are also known to inhibit HBV activity in vitro.
result support investigating the anti-HBV efficacy and safety of telbivudine in
HIV-HBV coinfected patients who do not require anti-HIV treatment, within [a]
clinical trial setting," they added.
Novartis Pharma AG, Basel,
Switzerlan; Novartis Institute for Biomedical Research, Cambridge, MA.
Avila, S Karwowska, C Lai, and T Evans. Telbivudine Shows No Activity against
8 Different Clinical HIV Isolates and 2 Multi-Drug Resistant HIV Isolates. 44th
Annual Meeting of the European Association for the Study of the Liver (EASL 2009).
Copenhagen, Denmark. April 22-26, 2009.
2009 MAIN PAGE
Conference on Retroviruses and Opportunistic Infections (CROI 2009)
by HIV and Hepatitis.com - February 8 - 11, 2009, Montreal
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of the 15th Conference on Retroviruses and Opportunistic Infections (CROI 2009)
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