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Drugs & Therapy Perspectives

, Volume 24, Issue 3, pp 1–4 | Cite as

Maraviroc: a guide to its use in HIV-1 infection

Drug and Profile Reports

Adapted from Drugs 2007; 67 (15): 2277–88[1]

What is the rationale for developing the drug?

Although much progress has been made in the treatment of HIV-1 infection, there is an ongoing need for new classes of antiretroviral agents. It has been known for >20 years that the CD4 receptor on T cells and macrophages is the main receptor utilized by HIV-1 for entry into the host cell.[1] More recently, the chemokine receptors CCR5 and CXCR4 were identified as essential coreceptors for HIV-1 entry. Generally, only viral strains that utilize the CCR5 coreceptor for entry (R5-tropic HIV-1 virus) are detected during early HIV-1 infection, whereas X4-tropic viruses, which utilize the CXCR4 coreceptor for host cell entry, tend to develop later on in infection in ≈50% of patients and often herald the onset of AIDS.[1]

The development of antiretroviral therapy utilizing CCR5 antagonism has been of particular interest since genetic evidence of a naturally resistant human population came to light.[1]...

Keywords

Maraviroc Enfuvirtide Delavirdine Tipranavir CCR5 Antagonist 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References

  1. 1.
    Carter N, Keating GM. Maraviroc. Drugs 2007; 67(15): 2277–88PubMedCrossRefGoogle Scholar
  2. 2.
    Dorr P, Westby M, Dobbs S, et al. Maraviroc (UK-427, 857), a potent, orally bioavailable, and selective small-molecule inhibitor of chemokine receptor CCR5 with broad-spectrum anti-human immunodeficiency virus type 1 activity. Antimicrob Agents Chemother 2005 Nov; 49(11): 4721–32PubMedCrossRefGoogle Scholar
  3. 3.
    European Medicines Agency. Celsentri: summary of product characteristics [online]. Available from URL: http://emea.europa.eu [Accessed 2007 Dec 7]
  4. 4.
    Westby M, Lewis M, Whitcomb J, et al. Emergence of CXCR4-using human immunodeficiency virus type 1 (HIV-1) variants in a minority of HIV-1-infected patients following treatment with the CCR5 antagonist maraviroc is from a pretreatment CXCR4-using virus reservoir. J Virol 2006 May; 80(10): 4909–20PubMedCrossRefGoogle Scholar
  5. 5.
    Lalezari J, Goodrich J, DeJesus E, et al. Efficacy and safety of maraviroc plus optimized background therapy in viremic ART-experienced patients infected with CCR5-tropic HIV-1: 24-week results from a phase 2b/3 study in the US and Canada [abstract no. 104bLB plus oral presentation]. 14th Conference on Retroviruses and Opportunistic Infections; 2007 Feb 25–28; Los Angeles (CA)Google Scholar
  6. 6.
    Nelson M, Fätkenheuer G, Konourina I, et al. Efficacy and safety of maraviroc plus optimized background therapy in viremic, ART-experienced patients infected with CCR5-tropic HIV-1 in Europe, Australia and North America: 24-week results [abstract no. 104aLB plus oral presentation]. 14th Conference on Retroviruses and Opportunistic Infections; 2007 Feb 25–28; Los Angeles (CA)Google Scholar
  7. 7.
    Lewis M, Simpson P, Fransen S, et al. CXCR4-using virus detected in patients receiving maraviroc in the phase 3 studies MOTIVATE 1 and MOTIVATE 2 originates from a pre-existing minority of CXCR4-using virus [abstract no. 56 plus poster and oral presentation]. XVI International HIV Drug Resistance Workshop; 2007 Jun 12–16; BarbadosGoogle Scholar
  8. 8.
    Westby M, Smith-Burchnell C, Mori J, et al. Reduced maximal inhibition in phenotypic susceptibility assays indicates that viral strains resistant to the CCR5 antagnoist maraviroc utilize inhibitor-bound receptor for entry. J Virol 2007 Mar; 81(5): 2359–71PubMedCrossRefGoogle Scholar
  9. 9.
    Selzentry™ (maraviroc tablets): US prescribing information. New York: Pfizer Inc., 2007 AugGoogle Scholar
  10. 10.
    Lalezari J, Mayer H. Efficacy and safety of maraviroc in antiretroviral treatment-experienced patients infected with CCR5-tropic HIV-1: 48-week results of MOTIVATE 1 [abstract no. H-718a]. 47th Interscience Conference on Antimicrobial Agents and Chemotherapy; 2007 Sep 17–20; Chicago (IL)Google Scholar
  11. 11.
    Proestel S. FDA analyses of maraviroc safety data [online]. Available from URL: http://www.fda.gov [Accessed 2007 Jul 23]
  12. 12.
    FDA Maraviroc Review Team. FDA cover memorandum [online]. Available from URL: http://www.fda.gov [Accessed 2007 Apr 25]

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© Adis Data Information BV 2008

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