We evaluated the long-term effects of the single
oral administration of a new CXCR4 antagonist,
KRH-3955, on elevation of white blood cell (WBC), neutrophil and lymphocyte counts in normal cynomolgus monkeys. In the monkeys treated with 0, 2, 20, 200 mg/kg of the compound, WBC, neutrophil and lymphocyte counts increased dramatically at 2 days
after treatment. This effect was dose-dependent, and these cell counts remained elevated 15 days after
drug treatment. Since neutrophils are the most abundant WBCs in circulation and bone marrow neutrophil exhaustion impairs the response to
bacterial infections, it is intriguing to exploit this pharmacological increase of neutrophils as a tool to address its influence on
viral infections in vivo. The SHIV
infection studies using the SHIV-KS661c/cynomolgus monkey model showed that a single
oral administration of
KRH-3955 (100 mg/kg) approximately 24 h before virus exposure did not prevent
infection, although it did prevent CD4 cell depletion in 3/3 monkeys. Furthermore, single
oral administration of the
drug 2 weeks before viral exposure rescued CD4 cells in 1/3 monkeys. This prevention of CD4 cell depletion was observed in both blood and lymphoid tissues. These results show that natural course of the SHIV
infection is modulated by artificial increase of neutrophils and lymphocytes caused by
KRH-3955 in the cynomolgus monkey model.