Maraviroc: A review of its use in hivinfection and beyond

Shawna M. Woollard, Georgette D. Kanmogne

Research output: Contribution to journalReview article

57 Citations (Scopus)

Abstract

The human immunodeficiency virus-1 (HIV-1) enters target cells by binding its envelope glycoprotein gp120 to the CD4 receptor and/or coreceptors such as C-C chemokine receptor type 5 (CCR5; R5) and C-X-C chemokine receptor type 4 (CXCR4; X4), and R5-tropic viruses predominate during the early stages of infection. CCR5 antagonists bind to CCR5 to prevent viral entry. Maraviroc (MVC) is the only CCR5 antagonist currently approved by the United States Food and Drug Administration, the European Commission, Health Canada, and several other countries for the treatment of patients infected with R5-tropic HIV-1. MVC has been shown to be effective at inhibiting HIV-1 entry into cells and is well tolerated. With expanding MVC use by HIV-1-infected humans, different clinical outcomes post-approval have been observed with MVC monotherapy or combination therapy with other antiretroviral drugs, with MVC use in humans infected with dual-R5-and X4-tropic HIV-1, infected with different HIV-1 genotype or infected with HIV-2. This review discuss the role of CCR5 in HIV-1 infection, the development of the CCR5 antagonist MVC, its pharmacokinetics, pharmacodynamics, drug–drug interactions, and the implications of these interactions on treatment outcomes, including viral mutations and drug resistance, and the mechanisms associated with the development of resistance to MVC. This review also discusses available studies investigating the use of MVC in the treatment of other diseases such as cancer, graft-versus-host disease, and inflammatory diseases.

Original languageEnglish (US)
Pages (from-to)5447-5468
Number of pages22
JournalDrug Design, Development and Therapy
Volume9
DOIs
StatePublished - Oct 1 2015

Fingerprint

HIV-1
Chemokine Receptors
Viral Drug Resistance
CXC Chemokines
CC Chemokines
Virus Internalization
CD4 Antigens
HIV-2
maraviroc
Graft vs Host Disease
Virus Diseases
United States Food and Drug Administration
Canada
Glycoproteins
Therapeutics
Pharmacokinetics
Genotype
Viruses
Mutation
Health

Keywords

  • AIDS
  • CCR5 antagonists
  • Chemokine receptors
  • Drug interactions
  • Human immunodeficiency virus
  • Mutations
  • Pharmacodynamics
  • Pharmacokinetics
  • Resistance

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science
  • Drug Discovery

Cite this

Maraviroc : A review of its use in hivinfection and beyond. / Woollard, Shawna M.; Kanmogne, Georgette D.

In: Drug Design, Development and Therapy, Vol. 9, 01.10.2015, p. 5447-5468.

Research output: Contribution to journalReview article

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