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On The Horizon: A Whole New Class of Drugs -- Entry Inhibitors

Part 1 (of 3)

May 2001

A note from The field of medicine is constantly evolving. As a result, parts of this article may be outdated. Please keep this in mind, and be sure to visit other parts of our site for more recent information!

There has been a big breakthrough in how to fight HIV. Discovering how HIV gets inside of T cells has led to new drugs that block the virus from hijacking a cell. We now know it takes three steps for the virus to get inside a cell, and scientists have developed drugs that interfere with each one of these steps. Some of these drugs are almost ready for drugstore shelves, others are being tested in people, and still others are in test tubes.

Because these drugs do not get into your cells, they will have very different side effects from the ones we use now. This is big news for people who need a change from their cocktails. Because these drugs are so different from any others, they will stop virus that is resistant to all of the drugs we have now. This may be lifesaving news for people who have used up all of their options.

The Three Steps

It takes three steps for HIV to get into a cell. First, the virus has to attach to the cell. Scientists have found drugs that stop this in the test tube. They will soon be tested in people.

Secondly, the virus must change its shape in order to insert itself into the T cell. It does this using two parts of the surface of the T cell. These parts of the cell are co- receptors called CXCR4 and CCR5. There are drugs that have already been tested in some people that actually stop the virus from using either of these parts of the cell.

The third and final step the virus must take to get into the cell is called fusion. The virus fuses with the cell wall. This happens very quickly, but new drugs have been found that interfere with this last step, even though it only occurs for a fraction of a second.

In other words, we have 'attachment inhibitors,' 'co-receptor inhibitors' and 'fusion inhibitors,' currently being tested. These inhibitors look promising in the laboratory when they are used together. Together it's like locking up ALL the doors and windows to your house to stop anyone from getting in.

The first of these entry inhibitors will soon be ready for the drugstore Shelf T-20, (Trimeris and Roche) a fusion inhibitor, is already in phase III testing. This means it is being tested in enough people to prove that it works and get a license from the FDA. It looks very powerful and works on people who have used up all their other options. Unfortunately, T-20 needs to be given with a needle, just like insulin for diabetes. It seems to have virtually no side effects so far except for irritation where the needle goes in.

So far, T-20 has been successful at helping people who have had many drug failures, but alone it will not be able to rescue people. It needs to be used with other drugs or possibly with other entry inhibitors when they become available.

There is already a cousin of T-20 called T-1249 that has been shown in the test tube to work on virus that has grown resistant to T-20. It is at an earlier stage of development than T-20.

In the Pipeline

Different companies are developing entry inhibitors. So far, six look very promising. For inhibiting attachment, we have a drug called PRO 542.

For co-receptor inhibition we have a drug called AMD3100 (that inhibits CXCR4) and we have PRO 140, TAK 779 and SCH.c and SCH-d for CCR5.

Each of these drugs is in development and we will see, over the next two years, more drugs that stop HIV from getting into cells.

This article was reviewed by Dr. Cal Cohen, Research and Medical Director of Community Research Initiative of New England.

For more information contact Search For A Cure or email us at

A note from The field of medicine is constantly evolving. As a result, parts of this article may be outdated. Please keep this in mind, and be sure to visit other parts of our site for more recent information!

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This article was provided by Search for a Cure. It is a part of the publication Reasons for Hope.
See Also
More on HIV Medications
More on HIV Drugs in Development