Evaluation of the lymphocyte trafficking drug FTY720 in SHIVSF162P3-infected rhesus macaques

Abstract

FTY720 causes retention of lymphocytes in lymphatic tissues. Previous studies revealed that FTY720 can decrease or eliminate chronic viral infections of mice. We address here whether therapeutic use of FTY720 in simian human immunodeficiency virus (SHIV)-infected rhesus macaques could also decrease viraemia. FTY720 was administered intravenously to three SHIV(SF162P3)-infected macaques at 39, 7 or 6 weeks of infection; three control macaques (47, 48 or 6 weeks of infection) did not receive drug. FTY720 was given at 0.004 mg/kg on days 0, 1, 2, 14, 15 and 16, followed by 0.1 mg/kg on days 28, 29, 30, 42, 43 and 44. Blood was collected seven times throughout and four times during 47 days of follow-up. Only the 0.1 mg/kg dose resulted in a reduction in mean blood CD4+ T cells and B cells (to 33% and 27% of pre-drug levels, P=0.0024 and 0.003, respectively). FTY720 treatment did not lead to significant deviations from the natural pattern of viral control. Plasma viraemia progressed from a range of 10(4)-10(2) copies/mL before treatment to 10(4)-temporarily undetectable levels on the last day of treatment. SHIV(SF162P3) was not eliminated, however, as plasma viraemia and proviral DNA persisted during the follow-up. No significant alterations in T cell activity were noted throughout the drug course. FTY720 administration had no detectable therapeutic effect at the doses and schedules outlined here, although blood CD4+ T cells and B cells were effectively reduced. Future work might reveal whether FTY720 could be beneficial in more pathogenic SHIV, simian immunodeficiency virus or HIV infections.