Assessing theoretical risk and benefit suggested by genetic association studies of CCR5: experience in a drug development programme for maraviroc

Antivir Ther. 2007;12(2):233-45.

Abstract

The proliferation of published gene association studies of the CCR5delta32 mutation is of relevance to drug development of a CCR5 antagonist for HIV, in highlighting potential safety concerns. We conducted an initial review of all non-HIV gene association studies of CCR5-delta32, followed by detailed meta-analyses in the three disease areas most commonly reported. Our review indicated no consistent evidence of increased risk of susceptibility to hepatitis C virus infection or multiple sclerosis among individuals with CCR5-delta32 mutation, and suggested treatment with a CCR5 inhibitor is unlikely to have related adverse effects. There was, however, evidence to suggest rheumatoid arthritis as a potential therapeutic target for a CCR5 antagonist. Clinical evidence would be required to confirm these findings.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adult
  • Arthritis, Rheumatoid / drug therapy
  • Arthritis, Rheumatoid / genetics
  • CCR5 Receptor Antagonists*
  • Cyclohexanes / adverse effects*
  • Drug Design*
  • Female
  • Genotype
  • HIV Fusion Inhibitors / adverse effects*
  • HIV Infections / drug therapy
  • HIV Infections / genetics
  • Hepatitis C / chemically induced
  • Hepatitis C / genetics
  • Humans
  • Male
  • Maraviroc
  • Multiple Sclerosis / chemically induced
  • Multiple Sclerosis / genetics
  • Mutation
  • Pharmacogenetics / methods*
  • Receptors, CCR5 / genetics*
  • Receptors, CCR5 / metabolism
  • Risk Assessment
  • Risk Factors
  • Triazoles / adverse effects*

Substances

  • CCR5 Receptor Antagonists
  • Cyclohexanes
  • HIV Fusion Inhibitors
  • Receptors, CCR5
  • Triazoles
  • Maraviroc