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.