150,000) potently inhibits HIV-1 entry and replication in both primary peripheral blood mononuclear cells and primary macrophages at concentrations that do not affect CCR5's chemokine receptor activity. CCR5 is a member of G-protein-coupled, seven transmembrane segment receptors, also known as C-C motif chemokine receptor-5. Acute HIV infection almost always involves virus binding to the CCR5 co-receptor, and, during advanced HIV disease, the virus may shift to the alternate CXCR4 receptor, but half of the virus still binds to the CCR5 co-receptor. When tested as single intravenous doses (ranging up to 5 mg/kg of body weight or three subcutaneous doses of up to 324 mg), viral loads reached their nadir by post-treatment day-12 and remained significantly reduced through day-29, with no dose-limiting toxicity. Although intravenously administered HIV drugs are unlikely to rival their orally available, smallmolecule counterparts (e.g., aplaviroc, vivriviroc, maraviroc, and SCH-C, or SCH 351125), PRO 140 nonetheless promises to be of great prophylactic value in lowering the risk of HIV infection in rape victims as well in other clinical settings. PRO 140 will also have enduring value as a tool for investigating the cellular mechanisms uderlying HIV infection.
