Antivirale Wirksamkeit des Chemokinrezeptorhemmstoffs 1,1’-bis-1,4,8,11-tetra-azazyklo-tetradekan bei Katzen mit feliner Immunschwächevirusinfektion
„Placebo-controlled double-blind treatment study in naturally Feline Immunodeficiency Virus-infected cats using the chemokine receptor inhibitor 1,1’-bis-1,4,8,11-tetraazacyclotetradekan (AMD3100)“ Antiretroviral efficacy of the bicyclam 1,1’-bis-1,4,8,11-tetraazacyclotetradekan (AMD3100) alone or in combination with the acyclic nucleoside phosphonate (R)-9-(2-phosphonylmethoxyethyl)adenine (PMEA) was investigated. Forty naturally FIV-infected cats were treated for a period of 6 weeks in a placebo-controlled double-blind study. Patients were randomly classified into 4 treatment groups, “Placebo”, “AMD”, “PMEA”, and “AMD/PMEA”. Placebo or the compounds AMD3100 (0,5 mg/kg body weight) and PMEA (10 mg/kg body weight) were administered subcutaneously twice a day or twice a week, respectively. Side effects of treatment with PMEA were a statistically significant decrease in the erythrocyte count, the hemoglobin concentration, the packed cell volume, and the number of neutrophil granulocytes. PMEA treatment caused a statistically significant improvement in the inflammation of the oral cavity. AMD3100 showed no clinical side effects. Serum magnesium levels decreased statistically significant with AMD treatment without causing clinical sings. Cats in the AMD group showed a statistically significant decrease of the proviral load. Therefore, AMD3100 had a clear antiviral efficacy against FIV. Side effects were not causing clinical sings and the bicyclam should be tested over a longer treatment period. Combination of both substances did not exacerbate side effects of either component. There was a decrease in proviral load in cats receiving only AMD3100 while no decrease was observed in combination with PMEA. PMEA-induced immunomodulation possibly inhibited the mechanism of action of AMD3100. T cell activation and proliferation of latently infected T cells were potentially stimulated during PMEA treatment leading to insufficient blockage of CXCR4 by AMD3100 that would prevent infection of additional cells.
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