New Drug Strategy Shows Promise Against HIV12/22/10
WEDNESDAY, Dec. 22 (HealthDay News) -- Scientists are reporting
early but promising results from a new drug that blocks HIV as it
attempts to invade human cells.
The approach differs from most current antiretroviral therapy,
which tries to limit the virus only after it has gained entry to
The medication, called VIR-576 for now, is still in the early
phases of development. But researchers say that if it is
successful, it might also circumvent the drug resistance that can
undermine standard therapy, according to a report published Dec. 22
Science Translational Medicine.
The new approach is an attractive one for a number of reasons,
said Dr. Michael Horberg, director of HIV/AIDS for Kaiser
Permanente in Santa Clara, Calif.
"Theoretically it should have fewer side effects [and indeed had minimal adverse events in this study] and there's probably less of a chance of mutation in developing resistance to medication," said Horberg, who was not involved in the study.
Viruses replicate inside cells and scientists have long known
that this is when they tend to mutate -- potentially developing new
ways to resist drugs. "It's generally accepted that it's harder for
a virus to mutate outside cell walls," Horberg explained.
The new drug focuses on HIV at this pre-invasion stage. "VIR-576
targets a part of the virus that is different from that targeted by
all other HIV-1 inhibitors," explained study co-author Frank
Kirchhoff, a professor at the Institute of Molecular Virology,
University Hospital of Ulm in Ulm, Germany, who, along with several
other researchers, holds a patent on the new medication.
The target is the gp41 fusion peptide of HIV, the "sticky" end
of the virus's outer membrane, which "shoots like a 'harpoon'" into
the body's cells, the authors said. The launch of this peptide is a
first step in the virus's bid to inhabit host cells.
Although there are two other drugs on the market, maraviroc and
T-20, which also prevent the virus from entering cells, they don't
target fusion peptides. That makes this trial the first time that
scientists have seen that fusion peptides are a worthwhile target
in the fight against HIV/AIDS.
And given that fusion peptides also provide a point of entry for
many other viruses, from measles to Ebola and hepatitis B and C,
scientists theorize that the strategy could be turned against these
illnesses as well.
The 18 patients with HIV in this small phase I/II trial took
either 0.5, 1.5 or 5 grams of VIR-576 a day for 10 days via
Those taking the highest dose saw a 95 percent reduction in
their average viral load, the amount of HIV in the blood, without
developing severe adverse effects.
"They were getting results that are similar to maraviroc and T-20 and certainly comparable to what's seen with intracellular drugs," Horberg said.
But the same factors that have limited the use of maraviroc and
T-20 are also likely to get in the way here as well, namely the
cost and the fact that they must be given by injection (because of
the large size of the molecule), he warned.
The needle-vs-pill hurdle is something patients and doctors have
to contend with in many settings, not just HIV, Horberg said. For
example, "we all know that insulin works great [in diabetic
patients] but the hard part is convincing patients to actually take
Hoping to get around the problem, the researchers are now
searching for a smaller molecule to do the same job.
"The next big step is to use the structure of VIR-576 and its viral target (the fusion peptide) to generate small molecule inhibitors that act by the same mechanism but are orally available," Kirchhoff said. "We will start to test the first compounds next year, but how long it will take such drugs make it to the market is impossible to say."
"The bottom line is, yes, any time that you can find a new mechanism to attack the virus -- and certainly if you can prevent the virus from getting into the host cells -- that's a really good thing. But this isn't near prime-time," Horberg concluded.
There's more on HIV/AIDS at the
U.S. Centers for
Disease Control and Prevention.
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