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. 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 &#xb1; 3.8% to 1.9 &#xb1; 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 &#xb1; 19 to 11 &#xb1; 10, P < .001; AMD3100 + PMEA group: 12 &#xb1; 17 to 3 &#xb1; 5, P < .05), but did not decrease proviral or viral load and caused anemia (RBC [&#xd7; 10(6) /&#x3bc;L] PMEA group: 9.07 &#xb1; 1.60 to 6.22 &#xb1; 2.16, P < .05; AMD3100 &#xb1; PMEA group: 8.80 &#xb1; 1.23 to 5.84 &#xb1; 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.