This is a Phase I safety and tolerance study of a novel new anti-HIV therapy. The objective of this trial is to determine the safety and pharmacokinetics of escalating doses of AMD-3100 in healthy volunteers. AMD-3100 (AnorMED, Inc.) is a novel antiretroviral compound, a bicyclam, whose mechanism of action differs from that of currently licensed antiretroviral drugs. In in vitro studies, AMD-3100 inhibits HIV replication after virus adsorption to cells, but before the reverse transcription step (De Clercq et al. 1994). Further, these studies showed that AMD-3100 inhibits the entry of HIV virus, both HIV-1 and HIV-2, into CD4+ T-cells and other cells in which the CXCR-4 receptor is used for entry. It did not inhibit the binding of ligands for the CCR5 chemokine receptor. Virus that enters by the use of the CXCR-4 receptor is thought to be responsible for the progression of HIV infection and the immunopathogenesis, which leads to AIDS. This inhibition of entry extends to the capability of AMD-3100 to block fusion of HIV infected cells with other CD4+ cells. This ability of AMD-3100 may help prevent pathogenesis caused by such events in the lymph nodes as well as the periphery.
Showing the most recent 10 out of 1014 publications
