title: Efficacy and adverse effects of the antiviral compound plerixafor in feline immunodeficiency virus-infected cats.
abstract: BACKGROUND
  Bicyclam derivatives inhibit feline immunodeficiency virus (FIV) replication through selective blockage of chemokine receptor CXCR4.
  
  
  OBJECTIVE
  CXCR4 antagonist plerixafor (AMD3100, 1,1'-bis-1,4,8,11-tetraazacyclotetradekan) alone or combination with adefovir (PMEA, 9-(2-phosphonylmethoxyethyl)adenine) safe and effective for treating FIV-infected cats.
  
  
  METHODS
  Forty naturally FIV-infected, privately owned cats.
  
  
  METHODS
  Prospective, placebo-controlled, double-blind clinical trial. Cats randomly classified into 4 treatment groups. Received AMD3100, PMEA, AMD3100 in combination with PMEA, or placebo for 6 weeks. Clinical and laboratory parameters, including CD4(+) and CD8(+) cell counts, FIV proviral and viral load measured by quantitative polymerase chain reaction (qPCR) evaluated. Additionally, FIV isolates from cats treated with AMD3100 tested for drug resistance.
  
  
  RESULTS
  FIV-infected cats treated with AMD3100 caused significant decrease in proviral load compared to placebo group (2.3 ± 3.8% to 1.9 ± 3.1%, of blood lymphocytes P < .05), but did not lead to improvement of clinical or immunological variables; it caused a decrease in serum magnesium concentration without clinical signs. No development of resistance of FIV isolates to AMD3100 found during treatment period. PMEA administration improved stomatitis (stomatitis score [degree 1 - 100] PMEA group: 23 ± 19 to 11 ± 10, P < .001; AMD3100 + PMEA group: 12 ± 17 to 3 ± 5, P < .05), but did not decrease proviral or viral load and caused anemia (RBC [× 10(6) /μL] PMEA group: 9.07 ± 1.60 to 6.22 ± 2.16, P < .05; AMD3100 ± PMEA group: 8.80 ± 1.23 to 5.84 ± 1.58, P < .001).
  
  
  CONCLUSIONS
  Administration of CXCR4 antagonists, as AMD3100, can induce reduction of proviral load and may represent viable treatment of FIV-infected cats. Combination treatment with PMEA not recommended.
authors.affiliation: Clinic of Small Animal Medicine, LMU University of Munich, Munich, Germany. hartmann@lmu.de
authors.forename: K
authors.initials: K
authors.lastname: Hartmann
authors.forename: C
authors.initials: C
authors.lastname: Stengel
authors.forename: D
authors.initials: D
authors.lastname: Klein
authors.forename: H
authors.initials: H
authors.lastname: Egberink
authors.forename: J
authors.initials: J
authors.lastname: Balzarini
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000818:Animals; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D001596:Benzylamines; D001772:Blood Cell Count / Q000662:veterinary; D002415:Cats; D000080027:Cyclams; D004311:Double-Blind Method; D004359:Drug Therapy, Combination / Q000662:veterinary; D016181:Feline Acquired Immunodeficiency Syndrome / Q000188:drug therapy* / Q000821:virology; D005260:Female; D006571:Heterocyclic Compounds / Q000627:therapeutic use*; D016089:Immunodeficiency Virus, Feline / Q000502:physiology*; D008297:Male; D063065:Organophosphonates / Q000627:therapeutic use*; D011446:Prospective Studies; D019718:Receptors, CXCR4 / Q000037:antagonists & inhibitors; D018709:Statistics, Nonparametric; D019562:Viral Load / Q000662:veterinary; D014779:Virus Replication / Q000187:drug effects
chemical_list: D019380:Anti-HIV Agents; D001596:Benzylamines; D000080027:Cyclams; D006571:Heterocyclic Compounds; D063065:Organophosphonates; D019718:Receptors, CXCR4; C053001:adefovir; D000225:Adenine; C088327:plerixafor