Hep B therapy generates resistance to HIV drugs
Entecavir (Baraclude), a drug used to treat chronic hepatitis B infection, has generated resistance mutations to anti-HIV drugs in at least three patients who were co-infected with both viruses. Before this, entecavir
had been thought to have no activity against HIV. The data were presented
at the 14th conference
on retroviruses and opportunistic infections in Los Angeles last week.
In all three instances the patient’s level of HIV infection was
not so advanced as to require treatment and the patients were started
on entecavir for hepatitis B (HBV). Over the course of normal monitoring,
the patients’ HIV viral loads dropped but on a subsequent visit
they had begun to climb again.
Using new, more sensitive assays, Johns Hopkins University researcher
Chloe Thio was able to demonstrate that entecavir did have activity against
HIV both in vitro and in vivo. The patients’ HIV was being treated
with an ineffective monotherapy and resistance to the drug quickly emerged.
Entecavir “selected for the M184V mutation that confers resistance
to lamivudine and emtricitabine, making them ineffective for treating
HIV”, she said.
Dr Thio believes that guidelines for treating HIV/HBV co-infection will
have to be changed to warn against use of entecavir if the patient is
not on a fully suppressive regimen for HIV. She is investigating whether
other anti-HBV drugs might have a similar effect in this patient population.
Bristol-Myers Squibb manufactures entecavir. Research vice-president
Rich Colonno said at the conference: “We have studied this drug
for over 10 years. We have assayed it against HIV probably thousands
of times now … .The only time we can see any activity is when we
use extremely low viral inoculates.” However, the company and the
US Food and Drug Administration have written to health care professionals
explaining that they have changed the label indication of the drug to
note the reported incidents and that entecavir has not been evaluated
in co-infected patients other than those simultaneously receiving highly
active antiretroviral therapy.
Entecavir has been available in the UK since September 2006.
Sonali Sonecha, lead pharmacist HIV services at North Middlesex Hospital,
London, speaking on behalf of the HIV Pharmacy Association, commented: “Although
the data are from a small number of patients, this information suggests
that in some co-infected patients, care needs to be taken when choosing
what drugs to use to treat HBV. As pharmacists, we should be advising
clinicians of the options available to treat HBV and the possible consequences
of each, so that treatment is tailored to the individual.”
|
The
Pharmaceutical Journal
Acrobat
Reader