What Are Integrase Inhibitors?
Integrase is one of three viral enzymes necessary for HIV replication. Integrase does what the name implies, it integrates (blends) HIV genetic material into the DNA of human CD4 cells. This blending of DNA makes it possible for the infected cell to make new copies of HIV. By interfering with integrase, the integrase inhibitors prevent HIV genetic material from integrating into the CD4 cell, thus stopping HIV replication.Understanding the Steps of HIV Replication
Why Are Integrase Inhibitors Important?
As we talked about earlier, integrase inhibitors are a new class of HIV medication. They will target a new step in the HIV life cycle. Because they target new life cycle steps, even the most drug-experienced HIV patient should benefit from integrase inhibitors. In other words, because integrase inhibitors target HIV differently than existing HIV medications, most HIV+ people will benefit from integrase inhibitors to some degree. For those patients with an extensive HIV medication history or HIV resistance, integrase offers them a brand new option.
Facts About Isentress (raltegravir)
Much needs to be learned abut a drug before the FDA allows it to be prescribed and sold commercially. Clinical trials and studies put the new drug through its paces to evaluate how well it works, at what dose it works best, and finally at what dose is it safe to be taken. Through the clinical trial process, we have learned quite a bit about Isentress.
- The dosing will most likely be twice each day along with other existing HIV medications as part of a HIV drug regimen.
- Like most medications there is the potential for interaction with other medications including some HIV medications.
- Because it is a new class of drug, most all HIV patients who take Isentress should benefit to some degree from the drug.
- In clinical trials, those taking Isentress showed decreased viral load counts and increased CD4 counts.
- In studies, the most common side effects were headache and diarrhea.
- During studies, the drug did not affect cholesterol and triglyceride levels like some HIV medications.
- Isentress actually has a low barrier to resistance meaning only a few mutations are needed to generate resistance. Because of this, doctors will prescribe Isentress with other drugs they know the patient hasn't developed resistance to. For instance, there is talk about prescribing Isentress with Maraviroc in patients with multi-drug resistance, knowing that those two drugs should be effective.
- Some doctors may hold off starting Isentress until they can pair it with a drug that the patient's particular virus is not resistant to.
Understanding the Road to FDA Drug Approval
What Comes Next?
The FDA panel that has reviewed the Isentress data has suggested it be approved under the accelerated six-month review process. If that is the case, Isentress should be considered for approval by the FDA sometime in October 2007. Once approved, Merck has estimated that Isentress could generate about $1 billion in annual sales.
Approval With Caution
Last month, the FDA approved Pfizer's new drug Selzentry (maraviroc) despite concerns over potentially fatal liver toxicity in some people taking the drug. The FDA approved the drug with the understanding that Pfizer would do follow-up studies after the drug's approval to make sure concerns over liver toxicity are monitored and addressed. Some have suggested that Isentress may be in store for something similar. However, the need to approve Isentress with conditions will be decided when the FDA meets in October.Pfizer's Newest Drug Maraviroc
Use About.com's Drug Finder for more information on Isentress and Selzentry.
Sources:
AIDSmeds.com; "Isentress Fact Sheet"; 28 Jun 2007.
Zimm, A. and Lopatto, E.; "Merck's Isentress AIDS Pill Recommended by U.S. Panel"; Bloomberg.com; 5 Sept 2007.
