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Fact Sheets Maraviroc (Celsentri) SummaryMaraviroc is a type of anti-HIV drug called a CCR5 antagonist or entry inhibitor. Common side effects of maraviroc can include cough, fever, muscle pain and rash. The dose of maraviroc used depends on the other medications in your combination. Maraviroc can be taken with or without food. What is maraviroc?Maraviroc, sold under the brand name Celsentri (also known as Selzentry), is a type of anti-HIV drug (antiretroviral) drug called a CCR5 antagonist or entry inhibitor. Maraviroc is used in combination with other anti-HIV drugs to treat, but not cure, HIV/AIDS. How does maraviroc work?Most currently approved therapies for the treatment of HIV infection work by interfering with HIV after it has infected a cell. Maraviroc is different because it acts before HIV has infected a cell. Maraviroc works by covering a molecule called CCR5 that is found on the surface of cells of the immune system. HIV needs to attach itself to CCR5 in order to enter and infect a cell. Maraviroc blocks access to CCR5 so HIV cannot get in, hence it belongs to a class of anti-HIV drugs called entry inhibitors. By using maraviroc as part of combination therapy, HIV’s ability to infect cells is reduced and production of new copies of HIV is also greatly reduced. Know your co-receptorsHIV needs a number of different receptors to help it enter and infect a cell. The first of those receptors is called CD4. This receptor is found on many cells of the immune system, including T-cells and macrophages. But HIV also needs at least one of two co-receptors—CXCR4 (or X4) and CCR5 (or R5)—to help it get into a cell. HIV that prefers R5 receptors is called R5 tropic and HIV that prefers X4 receptors is called X4 tropic. Some forms of HIV can attach to either receptor; these viruses are called dual or mixed tropic. To help assess which kind of virus predominates in a person, the company Monogram Biosciences has developed a tropism test called Trofile. Using this test, a sample of blood can be analysed to find out the tropism of HIV. Before using maraviroc, a Trofile test must be performed on a patient’s blood sample to help physicians decide whether maraviroc is going to work. More about the Trofile assayIn order to profile the co-receptor tropism, maraviroc users will have their blood assessed with Trofile prior to starting therapy with this drug. This is an important step because some people have HIV that prefers to use CXCR4 or both CXCR4 and CCR5. Maraviroc only works against HIV that prefers to use CCR5, so the screening test with Trofile helps doctors decide who will benefit from the use of maraviroc. Trofile results can be as follows:
How do PHAs use maraviroc?Maraviroc is used in combination with several other anti-HIV drugs, usually nukes (nucleoside analogues), non-nukes (NNRTIs) and drugs from other groups (classes) such as protease inhibitors. Combinations such as this are called highly active antiretroviral therapy, or HAART. For more information on HAART, see CATIE's Practical Guide to HAART for People Living with HIV/AIDS at www.catie.ca/PG_HAART_e.nsf. For many people with HIV/AIDS (PHAs), the use of HAART has increased their CD4+ cell counts and decreased the amount of HIV in their blood (viral load). These beneficial effects help to reduce the risk of developing a life-threatening infection. Neither maraviroc nor any other anti-HIV medication is a cure for HIV/AIDS. It is therefore important that you do the following:
Before starting maraviroc, potential users have a sample of their blood sent for a Trofile test. Trofile is an expensive test, costing hundreds of dollars. However, because the use of maraviroc depends on knowing a person’s HIV co-receptor preference, Pfizer is paying for the cost of Trofile in Canada. Trofile is expected to be available in major treating centres across Canada. WarningsBear in mind that maraviroc is a relatively new medication. The full range of its side effects may not be known for many years. 1. Liver healthLiver damage has occurred in some people who have used maraviroc. In some cases, an allergic reaction has occurred before the liver was damaged. The following symptoms can accompany the allergic reaction:
If these occur, contact your doctor right away. 2. Infections and cancerIn theory, it is possible that maraviroc and similar drugs may affect the immune system, increasing the risk of developing infections and possibly, cancer. In studies with people given maraviroc, there appeared to be a slightly increased risk of herpes infections. The manufacturer recommends that people taking maraviroc need to be monitored for symptoms of infection. There were no reports of an increased risk of cancer with maraviroc in studies with people for one year. The long-term risks of exposure to maraviroc are not known. Side effects1. GeneralCommon side effects that have been reported by some maraviroc users include the following:
2. CardiovascularAccording to the manufacturer, maraviroc should be “used with caution” in patients with a history of cardiovascular disease or who are at risk for a heart attack, stroke or another cardiovascular-related complication. Maraviroc should also be used with caution in people who have low blood pressure or who are taking medication to lower their blood pressure. People who have low blood pressure and who use maraviroc may experience dizziness or fainting when they stand up. 3. HepatitisMaraviroc has not been well studied in people co-infected with HIV and hepatitis-causing viruses such as hepatitis B virus or hepatitis C virus. These viruses cause liver damage and if liver disease grows worse while on maraviroc, the manufacturer notes that doctors must consider interrupting or stopping the use of maraviroc. 4. PregnancyIf you are pregnant or want to have a baby, tell your doctor. The manufacturer recommends that maraviroc should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. 5. Lipodystrophy syndromeThe HIV lipodystrophy syndrome is the name given to a range of symptoms that can develop over time when people use HAART regimens. Some features of the lipodystrophy syndrome include:
Together with these physical changes, lab tests of your blood may detect the following:
The precise causes of the HIV lipodystrophy syndrome are not clear and are difficult to understand because in some PHAs there may be one or more aspects of the syndrome taking place. For instance, some people may experience fat wasting, others fat gain, and others may experience both fat gain and wasting. What is becoming increasingly clear is that unfavourable changes in the lab readings of glucose, cholesterol, and triglycerides over a period of several years increase the risk of diabetes and cardiovascular disease. So far, however, the many benefits of HAART are much greater than the increased risk of cardiovascular disease or other side effects. Maintaining a normal weight, eating a healthy diet, exercising regularly and quitting smoking are all important in helping you to reduce your risk of diabetes, heart disease, and other complications. Regular visits to your doctor for checkups and blood tests are a vital part of staying healthy. If necessary, your doctor can prescribe lipid-lowering therapy. Researchers are studying the lipodystrophy syndrome to try to discover ways of helping PHAs avoid or reduce this problem. To find out more about options for managing aspects of the lipodystrophy syndrome, see CATIE's Practical Guide to HIV Drug Side Effects at www.catie.ca/sideeffects_e.nsf. Drug interactionsAlways consult your doctor and pharmacist about taking any other prescription or non-prescription medication, including over-the-counter medicines, herbs, supplements, and street drugs. Some drugs can interact with maraviroc, increasing or decreasing its levels in your body. Increased drug levels can cause you to experience side effects or make pre-existing side effects worse. On the other hand, if drug levels become too low, HIV can develop resistance and your future treatment options may be reduced. If you must take a drug that has the potential to interact with your existing medications, your doctor can do the following:
Drug interactions with maravirocMaraviroc has the potential to interact with many commonly used medications. The manufacturer has made relevant suggestions when different medications are used at their standard doses with maraviroc. There are several lists in this fact sheet about dose adjustments; bear in mind that these lists are not exhaustive. Non-nukes
Protease inhibitors
Non-nukes and protease inhibitors
Other combinations of anti-HIV medications
Antifungal agents
Antibiotics
Erectile dysfunction agents
Resistance, cross-resistance and treatment interruptionOver time, as new copies of HIV are made in the body, the virus changes its structure. These changes are called mutations and can cause HIV to resist the effects of anti-HIV drugs, which means those drugs will no longer work for you. Combining maraviroc with at least two other anti-HIV drugs delays the development of drug resistance. To reduce the risk of developing drug resistance, all anti-HIV drugs should be taken every day exactly as prescribed and directed. If doses are delayed, missed, or not taken as prescribed, levels of maraviroc in the blood may fall too low. If this happens, resistant virus can develop. If you find you are having problems taking your medications as directed, speak to your doctor and nurse about this. They can find ways to help you. When HIV becomes resistant to one drug in a class, it sometimes becomes resistant to other drugs in that class. This is called cross-resistance. Feel free to talk with your doctor about your current and future treatment options. To help you decide what these future therapies might be, at some point your doctor can have a small sample of your blood analysed using resistance testing. Should HIV in your body become resistant to maraviroc, your doctor, with the help of resistance testing, can help put together a new treatment regimen for you. There are other CCR5 receptor blockers in development. It is not clear if HIV resistant to maraviroc will be sensitive to these other receptor blockers. Dosage and formulationsMaraviroc (Celsentri) is available in 150 and 300 mg tablets. The dose of maraviroc used depends on the other medications in your combination; check the “Drug interactions with maraviroc” section for more specific information. Formulations can change, and dosages may need to be customized. All medications should always be taken as prescribed and directed. AvailabilityMaraviroc is licensed in Canada for the treatment of HIV infection in adults, in combination with other anti-HIV drugs. Your doctor can tell you more about the availability and coverage of maraviroc in your region. CATIE’s online module Federal, Provincial and Territorial Drug Access Programs (on CATIE’s website at www.catie.ca/eng/Publications/drugaccess/drugaccessIndex.shtml) also contains information about Canadian drug coverage. ReferencesAjuebor MN, Wondimu Z, Hogaboam CM, et al. CCR5 deficiency drives enhanced natural killer cell trafficking to and activation within the liver in murine T cell-mediated hepatitis. American Journal of Pathology 2007;170(6):1975-1988. Cornwell PD and Ulrich RG. Investigating the mechanistic basis for hepatic toxicity induced by an experimental chemokine receptor 5 (CCR5) antagonist using a compendium of gene expression profiles. Toxicologic Pathology 2007;35(4):576-588. Gulick RM, Su Z, Flexner C, et al. Phase 2 study of the safety and efficacy of vicriviroc, a CCR5 inhibitor, in HIV-1-Infected, treatment-experienced patients: AIDS clinical trials group 5211. Journal of Infectious Diseases 2007;196(2):304-312. Holst PJ, Orskov C, Qvortrup K, et al. CCR5 and CXCR3 are dispensable for liver infiltration, but CCR5 protects against virus-induced T-cell-mediated hepatic steatosis. Journal of Virology 2007;81(18):10101-10112. Lalezari J, Goodrich J, DeJesus E, et al. Efficacy and safety of maraviroc in antiretroviral experienced patients infected with CCR5-tropic HIV-1: 48-week results of MOTIVATE-1. Program and abstracts of the 47th Interscience Conference on Antimicrobial Agents and Chemotherapy, 17-20 September 2007, Chicago. Oral presentation H-718a. Pfizer Canada. Celsentri (maraviroc) tablets. Product monograph. 17 October 2007. Glass WG, McDermott DH, Lim JK, et al. CCR5 deficiency increases risk of symptomatic West Nile virus infection. Journal of Experimental Medicine 2006;203(1):35-40. Lasser KE, Allen PD, Woolhandler SJ, et al. Timing of new black box warnings and withdrawals for prescription medications. JAMA 2002;287(17):2215-2220. | |
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2008 Author(s): Hosein SR | |
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Decisions about particular medical treatments should always be made in consultation with a qualified medical practitioner who is knowledgeable about HIV-related illness and the treatments in question. MORE | |