Laboratory
Study Provides Details on Entecavir (Baraclude) Activity against Various Types
of HIV
By
Liz Highleyman At
the 2007 Conference on Retroviruses and Opportunistic Infections, researchers
reported that the
hepatitis B drug entecavir (Baraclude) is also active against HIV, and can
select for the M184V mutation, which confers resistance to the antiretroviral
agents lamivudine (3TC; Epivir)
and emtricitabine (Emtriva).
As a result of these findings, U.S. treatment guidelines were revised
to recommend that entecavir not be used alone by HIV-HBV coinfected individuals
who are not also receiving antiretroviral therapy for HIV. In fact, the latest
version of the guidelines advises that all HIV-HBV
coinfected people who need treatment for hepatitis
B should receive combination
HAART that includes agents active against both viruses.
Since 2007,
there have been several other reports on the anti-HIV activity of entecavir in
patients. At the XVII International AIDS Conference
this month in Mexico City, investigators presented a poster describing in vitro
activity of entecavir against various strains of HIV-1 and HIV-2.
In a
laboratory study, the researchers determined the susceptibility of 8 HIV-1 clades
or subtypes, various mutant viruses, and HIV-2 to entecavir,
zidovudine (AZT; Retrovir),
and lamivudine over 5 days in
cultured human peripheral blood mononuclear cells. Viral RNA was then extracted
and sequenced to look for resistance mutations. Results
•
Entecavir demonstrated
potent activity against HIV-2 and HIV-1 clade B and subtype O (50% effective concentration
[EC50] < 1 µM).
•
The drug exhibited
moderate activity against HIV-1/LAI, clade A, and the recombinant clade A/E (EC50
2.6-5.5 µM).
•
It showed weak
activity against HIV-1 clades C, D, G, and subtype N (EC50 > 10 µM).
•
The fold increase
in EC50 was 0.15 for the mutations D67N, K70R, T215Y, and K219Q ("4xAZT")
and 0.18 for K65R.
•
The M184V mutation
alone conferred an EC50 fold increase of 22.5, while the combination of M184V+T215Y
showed a fold increase of 7.5.
•
Entecavir selected
for resistant HIV-1 containing the M184I and M184V mutations as early as week
7.
"These
data demonstrate for the first time that entecavir is active against HIV-1 clades
B, A, A/E, subtype O, mutants 4xAZT, K65R, as well as HIV-2, but not clades C,
D, G, and subtype N," the researchers concluded. As
anticipated, they added, "mutants M184V and M184V+T215Y conferred high-level
resistance to entecavir. Entecavir selected for the M184V mutation in peripheral
blood mononuclear cells as shown in humans receiving this drug." Emory
University and Veterans Affairs Medical Center, Decatur, GA.
8/29/08
Reference
MA
Detorio, KL Rapp, MR Cristiano, and others. Antiviral activity of entecavir against
various HIV-1 clades, drug resistant mutants and HIV-2 in human lymphocytes. International
AIDS Conference (AIDS 2008). Mexico City. August 3-8, 2008. Abstract TUPE0001. |
