Scientists are reporting early but promising results from a new drug that blocks HIV as it attempts to invade human cells.
Different From Other Therapies
The approach differs from most current antiretroviral therapy, which tries to limit the virus only after it has gained entry to cells.
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 in the journal Science Translational Medicine.
The new approach is an attractive one for a number of reasons, said Michael A. Horberg, MD, director of HIV/AIDS for Kaiser Permanente in Santa Clara, California.
"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 Dr. Horberg, who was not involved in the study.
Background
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," Dr. 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 coauthor Frank Kirchhoff, PhD, 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 gp 41 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.
Worthwhile Target
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.
Trial Details
The 18 patients with HIV in this small phase 1/II trial took either 05, 15 or 5 grams (g) of VIR-576 a day for 10 days via injection.
Those taking the highest dose saw a 95% 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 with what's seen with intracellular drugs," Dr. Horberg said.
Persistent Obstacle
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-versus-pill hurdle is something patients and doctors have to contend with in many settings, not just HIV, Dr. Horberg said. For example, "we all know that insulin works great (in patients with type 2 diabetes) but the hard part is convincing patients to actually take it."
Next Steps
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 VIR576 and its viral target (the fusion peptide) to generate small molecule inhibitors that act by the same mechanism but are orally available," Dr. Kirchhoff said. "We will start to test the first compounds next year, but how long it will take such drugs to 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," Dr. Horberg concluded
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