title: Clinical studies with chemokine receptor-5 (CCR5)-inhibitors.
abstract: OBJECTIVE
  To summarise recently published clinical studies of chemokine receptor-5 (CCR5)-blockers, including the small-molecule blocker, maraviroc (MVC) and CCR5-monoclonal antibodies for HIV. MVC may have immunomodulating properties through CCR5-blockade. MVC appears well tolerated and penetrates the central nervous system. For these reasons, MVC is being investigated in immunodiscordance, prevention of IRIS and in HCV-HIV co-infection. Novel techniques allow tropism assignment via sequencing of proviral DNA; this testing platform is being utilised in MVC switch studies in those with HIV viraemia below the level of quantification. MVC is being utilised in regimen intensification studies for HIV associated neurocognitive disease.
  
  
  RESULTS
  MVC has no anti-inflammatory activity in rheumatoid arthritis. MVC appears well tolerated in hepatitis virus co-infected patients and MVC-intensification in HCV-HIV co-infection suggests a favourable impact on liver fibrosis. Early pilot data suggests MVC intensification may have functional benefit in the CNS. There is a growing body of data on tropism testing using proviral DNA; this technology is being utilised in MVC switch studies. CCR5-monoclonal antibodies administered subcutaneously are promising in Phase II development.
  
  
  CONCLUSIONS
  The place of MVC as an anti-HIV drug in the switch setting and as an immunomodulator is yet to be fully determined.
authors: Department of Internal Medicine I, University of Bonn, Bonn, Germany.
authors: Christoph
authors: C
authors: Boesecke
authors: Sarah L
authors: SL
authors: Pett
mesh_terms: D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D000998:Antiviral Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D065100:CCR5 Receptor Antagonists; D060085:Coinfection / Q000188:drug therapy; D003510:Cyclohexanes / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D006678:HIV / Q000235:genetics / Q000502:physiology; D015483:HIV Antibodies / Q000009:adverse effects / Q000627:therapeutic use; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy*; D019698:Hepatitis C, Chronic / Q000188:drug therapy; D006801:Humans; D000077592:Maraviroc; D025202:Molecular Diagnostic Techniques / Q000379:methods; D014230:Triazoles / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D056189:Viral Tropism; D014773:Virology / Q000379:methods
chemical_list: D000911:Antibodies, Monoclonal; D000998:Antiviral Agents; D065100:CCR5 Receptor Antagonists; D003510:Cyclohexanes; D015483:HIV Antibodies; D014230:Triazoles; D000077592:Maraviroc