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CCR5: A New Option for Those Who Have None Left

By David Scondras

October 2005

For people whose HIV treatment regimens have failed them, the development of new therapies is a race with life and death.

Although there are many HIV medications in development, most work in ways similar to today's medications. One medication that works completely differently is called a CCR5 antagonist. Three pharmaceutical companies -- GlaxoSmithKline, Schering-Plough and Pfizer are all competing to develop the first CCR5 antagonist.

Studies show these drugs are not only powerful, but they successfully fight virus resistant to all the other kinds of drugs currently available. Because this class of drugs might be more powerful when used together, it is not a waste of time for each company to develop its own.

CCR5 antagonists are very different from any other kind of HIV medicine and because of this, might have some special uses as well as some special problems.

Each of the three companies has already studied CCR5 antagonists in people with HIV. Unfortunately, studies in HIV-positive people who have never taken any HIV drug have been halted for the GlaxoSmithKline CCR5 drug, Aplaviroc. This is because during the study of Aplaviroc two HIV-positive volunteers who had never before used HIV drugs developed serious liver toxicity.

GlaxoSmithKline, however, is continuing to study Aplaviroc in people who have used many HIV drugs, since none of these people has had a bad reaction.

The other two CCR5 drugs in development, Pfizer's Maraviroc and Schering-Plough's Vicriviroc have not shown any signs of this problem so far.


Where CCR5 Drugs Came From and How They Work

When HIV enters your body, HIV hijacks an important white blood cell that is critical to your immune system. This cell is called a CD4 positive T lymphocyte or more easy to remember, a "T helper cell". HIV then teaches these cells to make more HIV.

The first thing HIV must do to hijack a cell is get inside the cell. To get inside takes several steps. One of those steps almost always uses a little part of the surface of the T cell. This part is called a CCR5 receptor. Scientists know this because they discovered that people that are born without a CCR5 receptor are pretty much immune to HIV. Many of these people immune to HIV are descendants of survivors of the bubonic plague.

If you are interested in the whole story of the connection between the bubonic plague and resistance to HIV, check out the Public Television Program notes "Secrets of the Dead" by clicking here.

The discovery that CCR5 receptors were critical for HIV's ability to enter the T cell taught scientists two things:

  1. Blocking the CCR5 receptor might stop HIV from hijacking cells.
  2. Since people born without CCR5 receptors are healthy, a medicine that blocks the CCR5 receptor probably wouldn't hurt anyone.


Two Different Kinds of Virus

Most HIV uses the CCR5 receptor to help it get inside a T cell. HIV that uses the CCR5 receptor to help it get inside a T cell is commonly called R5 virus. A less common type of HIV uses another receptor called a CXCX4 receptor to get inside a cell. This is called X4 virus.

One thing doctors were afraid of when the studies of CCR5 antagonists began is that these new medicines would turn HIV into the X4 virus. This was bad because the X4 virus is worse than R5 virus.

However studies show this does not happen. If someone already has X4 virus, the CCR5 antagonists do not work. But CCR5 antagonists do not turn HIV into X4 virus.

However, this does mean that people who have the X4 virus might not benefit from CCR5 antagonists. This is particularly unfortunate for people who are have advanced HIV disease, since many people with advanced HIV disease have X4 virus.


Using CCR5 Antagonists as Prophylaxis

It is possible that CCR5 antagonists are particularly good at protecting people from getting HIV immediately after exposure or even before exposure. Protecting people from getting HIV after they have been exposed to it is called "post exposure prophylaxis" or PEP.

Protecting people from getting HIV before they are exposed is called "pre-exposure prophylaxis" or PREP.

PEP for HIV is often used because health care workers occasionally get stuck with a needle with HIV-infected blood inside. For many years now HIV medications have been used to protect them from getting HIV and have been successful.

Using antiretrovirals to protect an unborn baby from getting HIV from an HIV-positive mother also works quite well.

Many scientists feel the CCR5 antagonists will be better at protecting people from HIV than other HIV medications because they work by stopping HIV before it even gets into a cell. If you can stop the virus from even getting into a cell in the first place, it might be a lot easier to protect a person from getting infected.

Someday we may have CCR5 antagonists used in microbicides (lubricants that can protect people from HIV during sex) or oral use of CCR5 antagonists for both pre and post exposure prophylaxis.


Hope

Many people are using up their HIV treatment options due to HIV drug resistant virus. Because it is a totally new class of HIV drugs, CCR5 antagonists will work where other drugs have failed. Developing new drugs like CCR5 means life for those who have run out of options. If you need this drug, there are seven clinical trials enrolling. You can find out more by at the internet site: www.clinicaltrials.gov/ct/search?term=HIV+CCR5

If there are no hitches, the drug will get approved within the next two years.

Good news for everyone.




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