What is Maraviroc used for?

**Introduction to Maraviroc**

Maraviroc, commercially known under trade names such as Selzentry in the United States and Celsentri in Europe, stands as a significant addition to the arsenal of treatments against HIV infection. Developed by Pfizer, this drug is classified as a CCR5 antagonist, a novel mechanism among antiretrovirals. While traditional HIV medications predominantly target the virus itself, either by inhibiting its enzymes or interfering with its replication, maraviroc works by blocking the CCR5 co-receptor on human T-cells. This receptor is essential for certain strains of HIV to enter host cells. By preventing the virus from latching onto these receptors, maraviroc effectively halts the progression of the infection.

Approved by the FDA in 2007, maraviroc offers hope for individuals who have developed resistance to other HIV medications. It is primarily indicated for treatment-experienced patients with evidence of CCR5-tropic HIV-1, meaning the strain of HIV that uses the CCR5 co-receptor to infect cells. The drug has undergone extensive research and multiple clinical trials demonstrating its efficacy in combination with other antiretrovirals. Despite its innovative approach, it is crucial to understand that maraviroc is not a cure for HIV but part of a lifelong management strategy.

**Maraviroc Mechanism of Action**

Maraviroc employs a unique mechanism to counteract HIV, setting it apart from other classes of antiretrovirals. The HIV virus typically enters a host cell by binding to both the CD4 molecule and a co-receptor, either CCR5 or CXCR4. Maraviroc specifically targets the CCR5 co-receptor, which is utilized by certain strains of HIV, known as R5-tropic HIV-1. By binding to the CCR5 receptor, maraviroc induces a conformational change that prevents the viral envelope from fusing with the host cell membrane. Consequently, the virus is unable to inject its genetic material into the host cell, thereby blocking the replication cycle at a very early stage.

This mode of action is vital for patients who harbor resistant strains of HIV, as it provides an alternative pathway to manage the infection. It is essential to note, however, that maraviroc is only effective against CCR5-tropic HIV-1. Before initiating therapy, patients must undergo a tropism test to ensure that their HIV strain predominantly uses the CCR5 receptor for entry. If the virus utilizes the CXCR4 receptor or both CCR5 and CXCR4 receptors (dual/mixed tropism), maraviroc will not be effective.

**How to Use Maraviroc**

Maraviroc is administered orally in the form of tablets. The standard dosage is typically 300 mg taken twice daily, although this can vary based on the patient's liver function, concurrent medications, and specific health conditions. Healthcare providers may adjust the dosage if the patient is taking other medications that either induce or inhibit the activity of liver enzymes responsible for metabolizing maraviroc.

The onset of action for maraviroc is relatively quick, with peak plasma concentrations reached within one to four hours after ingestion. However, the clinical benefits, such as suppression of viral load and improvement in CD4 cell counts, may take several weeks to become evident. It is crucial for patients to adhere strictly to the prescribed regimen to maintain effective drug levels in the blood and avoid the development of drug-resistant strains of the virus.

Maraviroc can be taken with or without food, offering flexibility to patients. However, it is recommended to maintain consistency in timing and dietary habits to ensure optimal absorption and efficacy. Patients should follow the guidance of their healthcare provider regarding the administration of maraviroc and report any issues with adherence or side effects to ensure the best possible outcomes.

**What are Maraviroc Side Effects**

Like all medications, maraviroc is associated with a range of potential side effects. Commonly reported adverse effects include gastrointestinal issues such as diarrhea, nausea, and abdominal pain. Additionally, some patients may experience headaches, dizziness, and fatigue. These side effects are generally mild to moderate and tend to diminish as the body adjusts to the medication.

More severe side effects, although less common, can occur and warrant immediate medical attention. These include symptoms of liver toxicity, such as jaundice (yellowing of the skin or eyes), dark urine, and persistent nausea or vomiting. Maraviroc has a black box warning for hepatotoxicity, and liver function should be monitored regularly during treatment.

Other serious side effects may include cardiovascular issues, such as an increased risk of heart attack, particularly in patients with pre-existing cardiovascular conditions. Additionally, maraviroc may cause severe skin reactions and allergic responses, which can manifest as rashes, itching, or swelling.

Contraindications for maraviroc include severe renal impairment or end-stage renal disease, particularly in patients taking potent CYP3A inhibitors or inducers, as these can significantly alter the drug's metabolism. Patients with a history of severe liver disease or cardiovascular conditions should discuss the risks with their healthcare provider before starting maraviroc.

**What Other Drugs Will Affect Maraviroc**

Maraviroc's effectiveness and safety can be influenced by other medications, primarily due to interactions involving the cytochrome P450 enzyme system, specifically CYP3A4. Certain drugs can either increase or decrease maraviroc levels in the bloodstream, necessitating dosage adjustments or careful monitoring.

CYP3A inducers, such as rifampicin (used to treat tuberculosis) and certain anticonvulsants like carbamazepine and phenobarbital, can reduce the effectiveness of maraviroc by accelerating its metabolism. In such cases, higher doses of maraviroc may be required to maintain therapeutic levels.

Conversely, CYP3A inhibitors, including protease inhibitors (like ritonavir) and antifungal agents (such as ketoconazole), can increase maraviroc levels by slowing its metabolism. This necessitates a lower dose of maraviroc to avoid potential toxicity.

Other drugs that may interact with maraviroc include certain antibiotics, such as clarithromycin, and calcium channel blockers, like diltiazem. Patients should inform their healthcare provider of all medications they are taking, including over-the-counter drugs and supplements, to avoid adverse interactions.

In conclusion, maraviroc represents a significant advancement in HIV treatment, particularly for patients with drug-resistant virus strains. Its unique mechanism of action, targeting the CCR5 co-receptor, offers an alternative pathway in managing HIV infection. However, the drug's administration, potential side effects, and interactions with other medications necessitate careful consideration and close monitoring by healthcare providers to ensure safety and efficacy.