Brand Name: Selzentry

Common Name: maraviroc (MVC, formerly UK-427,857)

Class: CCR5 antagonist (a type of entry inhibitor)

Standard Dose: Available in 150 mg and 300 mg tablets. 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 nukes; 600 mg twice daily if taken with Sustiva, Intelence, rifampin, and some anti-seizure medications. Default to the CYP3A inhibitor dose (the PI group) when using medications from different groups (such as a PI with a non-nuke). 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: $1,044/month for 150 mg or 300 mg tablets

Manufacturer contact: PPfizer Laboratories, www.Selzentry.com, 1-800-879-3477 (TRY-FIRST)

AIDSInfo: 1 (800) HIV–0440 (448–0440), www.aidsinfo.nih.gov

Most common include cough, fever, cold, rash, muscle and joint pain, stomach pain, and dizziness. Other potential side effects 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 include: low blood pressure when standing up that could lead to dizziness or fainting, diarrhea, edema (swelling), trouble sleeping, and urinary problems. Immune Reconstitution Inflammatory Syndrome (IRIS) may occur as the immune system regains strength; report symptoms of illness, such as shingles and TB, to 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.

Aptivus/Norvir, co-trimoxazole (Bactrim), and Viread have no interactions with Selzentry. Nizoral (ketoconazole), Kaletra, Norvir, Invirase, and Reyataz all increased Selzentry concentrations. Rifampin and Sustiva reduced Selzentry concentrations. Selzentry did not affect the concentrations of Versed (midazolam) and oral contraceptives.

Maraviroc is the first oral entry inhibitor available on the market. It is indicated for the treatment-experieced 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 one of 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 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 available at the time of writing, Pfizer did not find that blocking R5 with maraviroc caused virus to shift to X4 or show any other negative effect in so-called "dual tropic" people (their virus can use either R5 or X4). Last year the company reported that a switch to X4 or dual tropic virus was transient and reversible when people went off maraviroc. In the MOTIVATE studies, 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. Selzentry has been studied in treatment-naïve patients (first time on therapy) with less than impressive results. It was unable to match Sustiva at viral loads less than 50 copies. For now, this drug seems to be limited to treatment-experienced patients with CCR5-tropic virus.

Selzentry is another new entry inhibitor which blocks the ability of HIV to connect to what's called the CCR5 receptor, a key entry point for the virus. In studies Selzentry has proven itself very effective in people with advanced disease and high levels of drug resistance. To date it has had an excellent safety record, though there are some lingering doubts in this regard because it is the first drug of this type. Some scientists wonder whether there might be other consequences to blocking this CCR5 receptor, which is apparently used by the body in other ways that are not well known. Still, the data is the data, and to date it shows no evidence of any significant harm attributed to the drug. The drug's biggest drawback is the need to take an expensive test before using it. This drug is probably more useful than people give it credit for. It's highly potent, even in people with resistant virus, and shows little signs of toxicity. The biggest obstacle it faces is fear of the unknown. -- Martin Delaney