It was approved for medical use in the United States in August 2007,[2] and in the European Union in September 2007.[3]
Medical uses
Maraviroc is indicated, in combination with other antiretroviral medications, for the treatment of only CCR5-tropic HIV-1 infection.[2][3]
Side effects
Maraviroc can cause serious, life-threatening side effects. These include liver problems, skin reactions, and allergic reactions. An allergic reaction may happen before liver problems occur.[6] Official labeling of Selzentry has black box warning for hepatotoxicity.[2] The MOTIVATE trials showed no clinically relevant differences in safety between the maraviroc and placebo groups.[7]
Mechanism of action
Maraviroc is an entry inhibitor. Specifically, maraviroc is a negative allosteric modulator of the CCR5 receptor, which is found on the surface of certain human cells. The chemokine receptor CCR5 is an essential co-receptor for most HIV strains and necessary for the entry process of the virus into the host cell. The drug binds to CCR5, thereby blocking the HIV protein gp120 from associating with the receptor. HIV is then unable to enter human macrophages and T cells.[8] Because HIV can also use other coreceptors, such as CXCR4, an HIV tropism test such as a trofile assay must be performed to determine if the drug will be effective.[9]
History
Maraviroc, originally designated UK-427857, was developed by the drug company Pfizer in its UK labs located in Sandwich. On 24 April 2007 the U.S. Food and Drug Administration advisory panel reviewing maraviroc's New Drug Application unanimously recommended approval for the new drug,[10] and the drug received full FDA approval on 6 August 2007 for use in treatment experienced patients.[11]
Two randomized, placebo-controlled clinical trials, compared 209 people receiving optimized therapy plus a placebo to 426 people receiving optimized therapy plus 150 mg maraviroc once daily and 414 patients receiving optimized therapy plus 150 mg maraviroc twice daily. At 48 weeks, 55% of participants receiving maraviroc once daily and 60% of participants receiving the drug twice daily achieved a viral load of less than 400 copies/mL compared with 26% of those taking placebo; about 44% of the once-daily and 45% of the twice-daily maraviroc group had a viral load of less than 50 copies/mL compared with about 23% of those who received placebo. In addition, those who received the entry inhibitor had a mean increase in CD4+ cells of 110 cells/μL in the once-daily group, 106 cells/μL in the twice-daily group, and 56 cells/μL in the placebo group.[7][12][13] Maraviroc was approved for medical use in the European Union in September 2007.[3]
^ abStephenson J (April 2007). "Researchers buoyed by novel HIV drugs: will expand drug arsenal against resistant virus". JAMA. 297 (14): 1535–6. doi:10.1001/jama.297.14.1535. PMID17426263.
^Biswas P, Tambussi G, Lazzarin A (May 2007). "Access denied? The status of co-receptor inhibition to counter HIV entry". Expert Opinion on Pharmacotherapy. 8 (7): 923–33. doi:10.1517/14656566.8.7.923. PMID17472538. S2CID32675897.
^Emmelkamp JM, Rockstroh JK (October 2007). "CCR5 antagonists: comparison of efficacy, side effects, pharmacokinetics and interactions--review of the literature". European Journal of Medical Research. 12 (9): 409–17. PMID17933722.
^"Maraviroc reduces viral load in naive patients at 48 weeks". AIDS Patient Care and STDs. 21 (9): 703–4. September 2007. PMID17941136.
^World Health Organization (2005). "International nonproprietary names for pharmaceutical substances (INN): recommended INN: list 53". WHO Drug Information. 19 (1): 84–5. hdl:10665/73323. License: CC BY-NC-SA 3.0 IGO.