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Drug Warning Prompts Treatment Changes for those Infected with Hepatitis B And HIV - 06/20/2007

Drug Warning Prompts Treatment Changes for those Infected with Hepatitis B And HIV

Study identified risks for co-infected patients about taking entecavir
Release Date: June 20, 2007

Cross-resistance alarms raised earlier this year by Johns Hopkins
researchers about a widely used antiviral therapy for hepatitis B
liver infections have prompted swift treatment revisions by the
drug's maker and governmental agencies.

Findings by a team of Johns Hopkins infectious disease specialists,
to be published in the latest issue of The New England Journal of
Medicine online June 21, showed that entecavir should not be used on
its own in patients co-infected with HIV. Use of the drug led to
cross-resistance to certain antiviral drugs used to treat the AIDS virus.

As a result of the study's initial presentation in February at the
2007 Conference on Retroviruses and Opportunistic Infections (CROI),
Bristol-Myers Squibb, the drug's manufacturer, changed its product
labeling to warn of the potential for HIV drug resistance, notified
prescribing physicians and informed the U.S. Food and Drug
Administration. The U.S. Department of Health and Human Services
(HHS) also revised its treatment guidelines. HHS now recommends
against using entecavir, better known by its brand name Baraclude, as
the first option in treating hepatitis B in co-infected patients who
are not already using drugs to suppress HIV.

"Many co-infected patients and their physicians are justifiably
concerned about whether or not to use the drug," says senior study
author Chloe Thio, M.D.  She notes that more than 4 million people
worldwide are believed to be infected with both viruses.
"Patients contending with both diseases should consult with their
physician to see if entecavir is the right drug to treat their
hepatitis B in the first place, because the drug still works against
the liver disease, or if they should refrain from taking it because
of the potential for HIV drug resistance," says Thio, an associate
professor of medicine at the Johns Hopkins University School of Medicine.

Hepatitis B infection attacks the liver and can lead to cirrhosis,
liver cancer or even death from liver failure.

"Co-infected patients already on entecavir should consult with their
physician before stopping therapy and about having blood testing done
to monitor for any signs of drug resistance that could potentially
compromise subsequent anti-HIV therapy," she says.
In the published study, researchers documented three cases of
co-infected patients from Baltimore and San Diego who were only on
entecavir therapy, yet also had decreased amounts of HIV in their
blood, an indication that the drug could possibly be having some
impact on their HIV disease. Detailed blood analysis of two patients
showed that entecavir was interfering with HIV replication and
confirmed that one patient had developed the so-called M184V mutation
in HIV. This mutation is known to prevent two key drugs used to fight
the immune-system disease from working. Anti-HIV drugs compromised by
the mutation include lamivudine, better known as 3TC, and emtricitabine.

Since the results were presented at CROI, researchers have
substantiated their findings with several more cases from across the
United States, including some patients whose blood has tested
positive for the presence of the M184V.

Researchers say their next step is to better understand the mechanism
by which entecavir interferes with the enzyme, called reverse
transcriptase, which is involved in viral replication. Their goal is
to better understand how drug resistance develops, including the
M184V mutation. They also plan to look for evidence of any other HIV

A description of the original presentation is available on the Johns
Hopkins Web site

Entecavir, first marketed in March 2005, has been a leading treatment
for chronic forms of hepatitis B, which can be fatal to almost a
quarter of those infected if it is left untreated. More than 1.2
million Americans are infected with hepatitis B.

Other Johns Hopkins investigators involved in this research, which
was supported by funding from the National Institutes of Health, were
Moira McMahon, B.Sc.; Benjamin Jilek, B.Sc.; Timothy Brennan, M.S.;
Lin Shen, B.Sc.; Yan Zhou, Ph.D.; Megan Wind-Rotolo, Ph.D.; Sifie
Xing; Shridhar Bhat, Ph.D.; Robert Hegarty, C.R.N.P.; Curtis Chong,
B.Sc.; Jun Liu, Ph.D.; and Robert Siliciano, M.D., Ph.D.  Siliciano
is also a Howard Hughes Medical Institute investigator.  Additional
assistance from the Naval Medical Center in San Diego was provided by
Braden Hale, M.D.

For the Media

Media contact:

David March