Efficacy and Adverse Effects of the Antiviral Compound Plerixafor in Feline Immunodeficiency Virus‐Infected Cats

Abstract

Bicyclam derivatives inhibit feline immunodeficiency virus (FIV) replication through selective blockage of chemokine receptor CXCR4. 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. Forty naturally FIV-infected, privately owned cats. 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. 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). 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.