MaravirocEdit
Maraviroc is a selective antiretroviral medication that blocks the CCR5 chemokine receptor on human cells, preventing a subset of human immunodeficiency virus type 1 (HIV-1) from entering and infecting target cells. Marketed under the brand name Selzentry in the United States and Celsentri in other regions, maraviroc is approved for use in combination with other antiretrovirals for adults and certain pediatric patients with CCR5-tropic HIV-1 infection. Because many strains of HIV can use CCR5, CXCR4, or both co-receptors to gain entry to cells, a tropism test is typically required before initiating maraviroc therapy to ensure the circulating virus uses CCR5 CCR5 and is not CXCR4-tropic. If the virus is not predominantly CCR5-tropic, maraviroc is unlikely to be effective. For background, see HIV and Tropism as related topics.
Historically, maraviroc emerged as part of a broader effort to diversify the classes of drugs that can suppress HIV replication. It is part of the wider framework of {{antiretroviral therapy}} (ART), which combines drugs with different mechanisms to reduce viral load and restore immune function. In clinical practice, maraviroc is used as part of an optimized background regimen alongside other agents, rather than as a stand-alone cure. Its approval marked an important option for patients with resistance to other drug classes or with CCR5-t Tropism confirmed Trofile Tropism Test results. For regulatory and industry context, see FDA and EMA discussions of HIV therapies.
Mechanism of action
Maraviroc binds selectively to the CCR5 receptor on the surface of CD4+ T cells and other immune cells. By occupying this receptor, it prevents the HIV-1 envelope glycoprotein gp120 from engaging CCR5, thereby blocking receptor-mediated entry of CCR5-tropic virus into host cells. Because it targets a host protein rather than a viral protein, maraviroc’s antiviral activity is restricted to viruses that use CCR5 to enter cells. Viruses that utilize CXCR4 or that can switch co-receptor usage may not be susceptible to maraviroc, highlighting the importance of tropism testing prior to treatment initiation. See CCR5 and HIV for related background.
Medical uses
Maraviroc is indicated for adults with CCR5-tropic HIV-1 infection in combination with other antiretrovirals. It is also approved for certain pediatric patients, depending on regional labeling and the patient’s age and clinical status. The drug is not active against CXCR4-tropic viruses and therefore should not be used when tropism testing indicates CXCR4 usage or dual/mixed tropism. In practice, maraviroc is chosen when a patient’s virus is confirmed to be CCR5-tropic and when the treatment plan requires a regimen with a different mechanism of action or in the setting of resistance to other drug classes. For context on HIV treatment strategies, see Antiretroviral therapy and HIV.
Administration and pharmacokinetics
Maraviroc is taken orally and is primarily metabolized by the liver via the cytochrome P450 system, particularly CYP3A enzymes. Because of this metabolism, drug interactions with strong CYP3A inhibitors or inducers can necessitate dose adjustments and careful monitoring. Co-administration with certain medications can alter maraviroc exposure, and some combinations are contraindicated or require alternative regimens. Clinicians typically consider concomitant medications, liver function, and potential interactions when determining the final dosage. See CYP3A and drug interactions for related pharmacology concepts.
Safety, tolerability, and adverse effects
As with other antiretrovirals, maraviroc carries potential adverse effects. Common events seen in clinical practice include upper respiratory tract infections, cough, fever, rash, dizziness, and abdominal discomfort. A notable safety concern is hepatotoxicity; rare but serious liver injury can occur, so liver function monitoring is recommended, especially during the initial period after starting therapy or after dose changes. Other risks can include orthostatic effects, infections, or immune reconstitution phenomena in some patients. The risk-benefit profile of maraviroc should be weighed in the context of the patient’s overall ART plan, viral tropism, and co-existing conditions. See Hepatotoxicity and Adverse drug reaction for broader discussions of safety considerations in pharmacotherapy.
Tropism testing, resistance, and clinical use
Because maraviroc targets a host receptor rather than a viral component, its antiviral activity is contingent on the virus using CCR5 for cell entry. Baseline tropism testing is standard to confirm CCR5 usage before starting maraviroc; ongoing surveillance may be considered in certain circumstances if viral characteristics shift. Resistance to maraviroc is more likely if the virus uses CXCR4 or mixes of co-receptor usage; in such cases, maraviroc may lose its effectiveness. Clinicians also monitor for changes in viral load and CD4 counts as part of management. For a broader view of testing and resistance concepts, see Tropism and Drug resistance.
Regulatory history and policy considerations
Maraviroc was approved for clinical use in the United States in the late 2000s and has since been integrated into various treatment guidelines worldwide. Its development and market presence reflect the pharmaceutical sector’s emphasis on providing diverse mechanisms of action to address HIV’s evolving resistance patterns. The drug’s pricing, patent status, and access considerations often enter policy discussions, with stakeholders weighing the incentives for continuing innovation against the goal of broad patient access. See FDA and pharmaceutical patent discussions for related topics.
From a policy viewpoint, debates surrounding HIV therapies frequently touch on innovation incentives, cost containment, and the role of public funding in biomedical research. Proponents of a market-based approach emphasize patient choice, competition, and ongoing investment in new treatments, while critics may advocate for more aggressive pricing or policy tools to improve affordability. Advocates of cautious regulatory scrutiny argue that evidence-based therapeutic choices should guide formularies and coverage decisions, aiming to ensure real-world effectiveness and value. See Health economics and Public health policy for broader context.