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Here's how maraviroc and other entry inhibitors work
Expert offers nutshell explanation
Current entry inhibitors under study, including maraviroc, target one of the three stages of HIV's entry into cells.
In the first step, HIV's gp120, which is a glycoprotein, attaches itself to the CD4 protein (helper T-cells), which HIV particularly likes to destroy, explains W. David Hardy, MD, director of the Division of Infectious Diseases and the AIDS Program at Cedars-Sinai Medical Center in Los Angeles, CA. Hardy also is an associate professor of medicine in residence at the Geffen School of Medicine at the University of California -- Los Angeles.
"They're very important cells and are termed the conductor of the immunological orchestra," he says. "HIV attaches initially to the CD4 molecule, and there are some entry inhibitors working to disrupt that first attachment step, but those medications are still in clinical development and are not any where near licensure."
The second step is when HIV's gp120 attaches to the second human target called the CCR5 molecule, and once those two attachments have occurred, it allows the virus to stick to the outside of the cell, Hardy says.
"Once it's attached, there's a change that occurs in the virus that allows the virus to harpoon the human cells and cause fusion," he adds. "When the envelope of the virus and cell membrane fuse together the contents [of HIV] are pushed inside the cell."
In short, the three steps are as follows:
* Attachment of gp120 to human CD4 cell;
* Attachment of gp120 to human CCR5 cell;
* Fusion where cell membrane and viral envelope are fused together and attached.
The use of maraviroc, a new antiretroviral that is first in the CCR5 antagonist class, has helped push HIV treatment to an early step in the interaction of HIV and human cells, Hardy notes.
"It's very scientifically satisfying because the earlier we think we can stop the virus from attaching to the cell, the better it is," he says.