In August 2007, the U.S. Food and Drug Administration (FDA) approved Pfizer’s maraviroc, a new drug that fights HIV infection when combined with other HIV drugs. Maraviroc is an antiretroviral drug belonging to a new class of oral medications that act as entry inhibitors. Entry inhibitors block the HIV virus from entering white blood cells. The drug is for people with HIV who have not responded well to other HIV medications.
To enter white blood cells, HIV must first bind to the CD4 receptor and then to a co-receptor that is also on the surface of the cell. There are two co-receptors: CCR5 and CXCR4. Some strains of the virus use CCR5, others use CXCR4 and still others use both. Maraviroc blocks HIV’s ability to bind to the CCR5 co-receptor, preventing the virus from invading cells.
According to the FDA, maraviroc is not effective for all people with HIV. It only works for those whose virus uses the CCR5 co-receptor exclusively (rather than CXCR4 or a combination of both co-receptors). Among people who have previously received HIV antiretroviral medications, approximately 50% to 60% have the virus strain that uses the CCR5 co-receptor exclusively.
Antiretroviral medications prevent HIV infection by slowing down or halting the replication of HIV in the body. When HIV makes new copies of itself, it often makes mistakes. This means that within an infected person, there can be many strains of virus. Sometimes, a new strain is produced that is resistant to the effects of an antiretroviral drug. If the person is not taking other types of drugs, then the resistant strain is able to replicate quickly and the benefits of treatment are lost. Taking two or more antiretroviral drugs at the same time greatly reduces the rate at which resistance develops.
The FDA approved maraviroc in combination with other antiretroviral drugs for the treatment of adults who have been treated with other HIV medications, have elevated levels of HIV in their blood and whose virus uses the CCR5 co-receptor. “This is an important new product for many HIV-infected patients who have not responded to other treatments and have few options,” says Steven Galson, MD, MPH, director of the FDA’s Center for Drug Evaluation and Research.
The FDA’s accelerated approval of maraviroc is based on data from the ongoing MOTIVATE clinical trials, designed to test the drug and its effects on people with HIV. The double-blind studies were conducted on 1,076 participants. The drug belongs to the first new class of oral HIV drugs to become available in the US since the mid-1990s.
The FDA has given this drug a black box label, its highest level of warning. It recommends that the drug be used with caution in people who are co-infected with hepatitis B and C, who have pre-existing liver dysfunction or who are at increased risk for heart attack. Because maraviroc blocks the CCR5 co-receptor on some immune cells, there is an increased risk of developing infections and certain types of cancers.
Maraviroc (sold under the brand name Selzentry™) began shipping to pharmacies in mid-September 2007. There is no indication yet about how it will be covered by insurance companies.