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Keywords:

  • AMD3100;
  • Bicyclam;
  • CXCR4;
  • FIV

Background

Bicyclam derivatives inhibit feline immunodeficiency virus (FIV) replication through selective blockage of chemokine receptor CXCR4.

Hypothesis/Objectives

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.

Animals

Forty naturally FIV-infected, privately owned cats.

Materials and 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 < .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 [×106/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 and Clinical Importance

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.