GlaxoSmithKline has commenced Phase III clinical studies with its entry inhibitor aplaviroc (873140) in HIV treatment-experienced patients. Entry inhibitors like aplaviroc represent a new mechanism of action in this class of antiretrovirals. They work by binding to one of the chemokine co-receptors, CCR5, on the immune cell surface that is essential for HIV-1 entry and infection.

"The availability of an orally administered entry inhibitor may provide an important treatment option for people infected with HIV-1," Dr. Joseph Eron, Principal Director of the UNC AIDS Clinical Trials Unit said adding, "It is imperative that companies like GSK continue with their research and development efforts to expand the number of antiretroviral drugs available with different modes of action or improved efficacy and toxicity profiles."

Aplaviroc selectively inhibits the binding of the HIV envelope to the CCR5 co-receptor on the cell surface by producing changes in the receptor conformation via an allosteric mechanism. Allosteric inhibition occurs when an interaction in one region of a protein prevents the function of another part of the protein. This affects the interaction of the virus with the cell, as HIV cannot use the antagonist-bound CCR5 pathway. The viral entry cascade and subsequent infection by CCR5-using HIV are therefore blocked.