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Top Stories This Week in the Chronicle.
November 30, 2007

Two new drugs expand the
HIV treatment horizon

Dr. Barbara Gripshover, medical director of the John T. Carey Special Immunology Unit at University Hospitals, sat down to discuss the state of HIV treatment and the advances that are coming.

Julie Patterson: Youíve spent many years treating people living with HIV. What are you enthusiastic about currently in the HIV treatment world?

Barbara Gripshover: There are two new drugs, which work in new ways, which have just been approved by the Food and Drug Administration in the past few months: maraviroc (Selzentry), which is a CCR5 antagonist; and raltegravir (Isentress) which is an integrase inhibitor. These new drugs provide opportunities for patients who have been struggling with currently available drug combinations, especially due to resistance.

JP: You mentioned that these drugs work in new ways. Does that mean they are in entirely new classes of drugs?

BG: In the case of raltegravir, yes. Integrase inhibitors have been in development for years, but this is the first one available to the public.

Many people are familiar with drugs that work against two other enzymes in the HIV replication process: reverse transcriptase and protease.

This is the first time we can use a drug to block integrase, which is the enzyme that allows the genetic material of HIV to integrate with the genetic material (DNA) of the human CD-4 cell. If we block that integration, the virus cannot make new copies of itself.

JP: So CCR5 antagonists fit into a class of drugs that already exists?

BG: Well, yes, in a sense they do. CCR5 antagonists work in a unique way to block one of the co-receptors that HIV needs in order to enter a CD-4 cell. There is another entry inhibitor currently available that works in another way (T20 or Fuzeon), but both block entry and so are classified together. However since they block entry by different means, virus that is resistant to T-20 is still sensitive to maraviroc.

JP: Iíve heard that the CCR5 antagonists require a new lab test to determine if they will be effective for any given person. What can you tell me about it? Will the costs of the test be covered for patients?

BG: You are right. The lab test that is needed before prescribing a CCR5 antagonist is called a tropism assay. It is used to determine if an individualís virus uses CCR5 to enter the CD-4 cell, which is necessary if the CCR5 blocker, maraviroc, is going to work for that patient.

Some people have a version of the virus that can utilize a different co-receptor called CXCR4. In those people, a CCR5 antagonist will not be effective at blocking HIV from entering the CD-4 cell.

The test is expensive; therefore it is only ordered when maraviroc is being considered in a drug regimen for someone with multi-drug resistant virus. The test requires a detectable HIV viral load to be performed, similar to resistance tests.

JP: What do you like best about having these new drugs available?

BG: I like that that raltegravir is broken down by the body differently than most medications used to treat HIV. This means that it has fewer drug interactions when combined with other medications.

I also like that both maraviroc and raltegravir are approved for treatment-experienced patients who have HIV strains that are resistant to multiple antiretroviral drugs. They both hold promise for HIV-positive patients who no longer respond to other HIV drugs. These are the folks who are most in need of something new.

Lastly, I am always excited when more than one new drug comes on the market at a time because it allows patients to switch to a truly new regimen.

If only one drug is switched at a time, it may not work differently enough to really knock the virus down to the undetectable level that is our goal. With two new drugs, current drug resistance patterns can be overcome and patients are much more likely to have a good outcome.

With new classes of drugs, we are more likely to have drugs to which the virus is still susceptible, and that means I can offer patients renewed hope.

Barbara Gripshover, M.D., is an associate professor at Case Western Reserve University and medical director of the John T. Carey Special Immunology Unit of University Hospitals of Cleveland. She can be reached at 216-8445876 or

Julie Patterson, M.P.H. is community capacity building manager of the AIDS Taskforce of Greater Cleveland. She can be reached at 216-6210766 or



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