Selzentry
Common Name: maraviroc (formerly UK-427,857)
Brand Name: Selzentry
Class: CCR5 antagonist (a type of entry inhibitor)
Standard dose: without food, with no food restrictions. The recommended dose varies depending on other medications the patient is taking: 150 mg twice daily if taken with a protease inhibitor (except for Aptivus) and Rescriptor; 300 mg twice daily if taken with Aptivus, Viramune, Fuzeon, and all of the NRTIs; 600 mg twice daily if taken with Sustiva, Intelence, rifampin, and some anti-convulsant medications such as phenobarbital, phenytoin, and carbamazepine. Default to Selzentry 150 mg twice daily when combined with a CYP3A inhibitor dose (the PI group) if using medications from multiple classes (such as a PI with a NNRTI). Concurrent use of Selzentry and other medications that can either inhibit or induce liver metabolism will affect the dose of Selzentry. Your doctor or pharmacist can determine which medications will affect Selzentry.
AWP: $1,101.42 / month for 150 mg or 300 mg tablets
Manufacturer contact: ViiV Healthcare, 1 (877) 844-8872
Potential side effects and toxicity: Most common include cough, fever, cold, rash, muscle and joint pain, stomach pain, and dizziness. Other potential side effects may include liver toxicity; an allergic reaction may happen before the liver problems. It is recommended Selzentry be stopped and your doctor contacted right away if you develop a rash, yellowing of your eyes or skin, and/or dark urine, vomiting, and upper stomach pain. Other rare side effects may include low blood pressure when standing up that could lead to dizziness or fainting. Immune Reconstitution Inflammatory Syndrome (IRIS) may occur as the immune system regains strength; signs and symptoms of inflammation from previous infections may occur soon after anti-HIV treatment is initiated. Report symptoms of illness, such as shingles and TB, to a health care provider. While no increased risk of infections or cancer was seen in clinical trials, Selzentry affects other immune system cells and could possibly increase the risk of infections and cancer.
Potential drug interactions: Not recommended with rifampin or St. John’s wort. Dose adjustment needed for Biaxin, Dilantin (phenytoin), HIV NNRTIs and PIs, itraconazole, Mycobutin, Nizoral (ketoconazole), oral contraceptives, phenobarbital, rifampin, Tegretol (carbamazepine), Versed (midazolam), and Vfend.
Tips: Maraviroc is the first oral entry inhibitor available on the market. It is indicated for the treatment-experienced patient infected only with CCR5-tropic virus. Complex dosing, the need for an expensive tropism test, and competition from recently, or soon to be, approved drugs however, have dimmed some of the initial enthusiasm for this drug.
Viral tropism refers to the types of HIV that a person can have: CCR5-tropic (R5) virus and CXCR4-tropic (X4) virus. (Tropism is pronounced with a long “o,” as in “okay.”) HIV latches on to the CD4 receptor on the surface of some human T-cells (hence, CD4+ T-cells), and then it latches on to one of the two co-receptors on the surface of the cells, CCR5 (R5) or CXCR4 (X4). These two chemokine co-receptors basically invite HIV to come inside. As the name “CCR5 inhibitor” suggests, Selzentry inhibits (blocks) CCR5, shutting down this point of entry for the virus. (The co-receptor inhibitors are also called “antagonists,” as in “CCR5 antagonist.”) X4 virus is associated with advanced HIV disease. HIV infection may involve viruses that infect only CCR5 cells, only CXCR4, both of these types of cells (dual tropic), or a mix (mixed tropic). Most people are infected with CCR5 virus, and then over time more CXCR4 and mixed viruses accumulate. In results from various studies, Pfizer did not find that blocking R5 with maraviroc caused virus to shift to X4 or show negative effect on disease progression or CD4 count in so-called “dual tropic” people (their virus can use either R5 or X4). In 2007, the company reported that a switch to X4- or dual-tropic virus was transient and reversible when people went off maraviroc. In studies with treatment-experienced people, a large number of patients were excluded because they did not have exclusive CCR5-tropic virus, limiting the number of patients who could truly benefit from this drug. A sub-analysis reported that Selzentry seems to have minimal impact on lipid levels. Selzentry has been studied in treatment-naïve patients (first time on therapy) in the MERIT clinical trial. Although the initial analysis suggested that Selzentry was unable to match Sustiva at viral loads less than 50 copies, a re-analysis of the data using the enhanced Trofile test (Trofile ES) showed the regimens to be comparable (59% for Selzentry vs. 63% for Sustiva in less than 50 copies at 96 weeks). The follow-up results of 96-week data led to it’s FDA approval for this population. Other CCR5 inhibitors are in the works. Please see package insert for more complete potential side effects and interactions.
Doctor
Selzentry (maraviroc) was approved (one tablet twice daily without any food restriction) for use in combination with other antiretroviral drugs in the treatment of HIV infection in 2007. This antiretroviral is the first oral entry inhibitor produced. The mechanism of how it works is unique among other approved antivirals—it blocks a cell surface receptor called CCR5—which is one of two pathways that HIV uses on cell surfaces to attach to and subsequently enter cells. In someone who has a test showing their virus population uses CCR5, this drug is likely to be fully active. However, as with resistance testing, tests can miss very small amounts of virus populations that can use the other cell receptor (CXCR4), and this drug shows no activity in blocking those virus populations. While it was initially approved only for those who were already treatment-experienced, as it improves the rate of virologic suppression, re-analyses of the study done using maraviroc as part of a first regimen recently led to FDA approval for its use as part of the first combination. Nevertheless, there is ongoing ambiguity about the degree of enthusiasm for this drug as part of a first regimen. The 2009 DHHS guidelines state that there was insufficient data available at the time of writing their most recent update to decide what recommendation to offer for this drug for initial treatment. However, to date, it has been shown to be a safe drug with few side effect concerns. Maraviroc also interacts with a number of PIs and ritonavir and thus must be dose adjusted depending on the other antiretrovirals. —Cal Cohen, MD
Activist
The second comer to the entry inhibitor class, Selzentry is technically a CCR5-antagonist—meaning it only works against HIV that binds to the CCR5 receptor on T-cells. Finding out if you have this type of virus requires an expensive “tropism test” that may or may not be covered by your insurance. Add to that a complicated dosing depending on what other HIV meds you’re taking, and this becomes a drug that neither doctors nor patients want to bother with unless they have to. Unfortunately, the sickest patients who could benefit the most from this new drug are less likely to have the pure CCR5 virus that Selzentry would work against. —Jeff Taylor
