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Drugs! Drugs! Drugs!
An Overview of the Approved Anti-HIV Medications

Entry Inhibitors

Fall 2003/Winter 2004

Entry inhibitors work at HIV's first point of contact with a human cell. This occurs at an earlier stage in the HIV lifecycle than the other antiretrovirals. To successfully infect a cell, HIV needs to attach to and enter the cell through a series of steps. Proteins on the surface membrane of HIV (gp120 and gp41) interact with receptors on the surface of the cell (the CD4 receptor and a chemokine receptor, either CCR5 or CXCR4). Once this happens, a process called fusion occurs -- the membranes of the virus and the cell fuse together, allowing HIV's genetic material to enter the cell.

An entry inhibitor interferes with one of the steps in this process. It targets either one of the proteins on the surface of HIV or one of the receptors on the surface of the CD4 cell. So far, only one drug in this class, a fusion inhibitor called Fuzeon (enfuvirtide), has been approved, but several others are in development. Fuzeon blocks HIV's gp41 protein. With its gp41 occupied by the drug, HIV is unable to fuse with the CD4 cell and send its genetic material inside. Entry inhibitors in development interfere either with HIV's gp120 or gp41, or with one of the receptors on the CD4 cell, including CCR5 and CXCR4.

One of the biggest challenges with this class of drugs is that stomach acids break them down, so they can't be taken in an oral form. Like Fuzeon, many (but not all) entry inhibitors will need to be taken as an injection or by intravenous infusion.

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This article was provided by AIDS Community Research Initiative of America. It is a part of the publication ACRIA Update. Visit ACRIA's website to find out more about their activities, publications and services.
 

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