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GlaxoSmithKline begins phase III trials of new HIV drug



13th August,2005:GlaxoSmithKline (GSK) announced that phase III clinical studies with its entry inhibitor aplaviroc (873140) have commenced 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, the company said in an official release.

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.

GSK also hosted a satellite symposium at the 3rd International AIDS Society (IAS) Conference on HIV Pathogenesis and Treatment in Rio de Janeiro, Brazil, highlighting the company’s progress in the development of new treatments for HIV. Antiretroviral drug resistance is a major cause of treatment failure in patients infected with HIV-1 and has been associated with increased mortality. To address the continued need for new anti-HIV drugs, GSK has a number of drugs in development that hope to demonstrate activity against viral strains that are resistant to existing agents. In addition to aplaviroc, investigational compound 640385 is in phase II development as a next-generation protease inhibitor (PI); and 695634 is in phase II development as a next-generation non-nucleoside reverse transcriptase inhibitor (NNRTI). Both compounds are being evaluated for treatment of those patients whose virus has become resistant to multiple antiretroviral drugs.

Aplaviroc is the proposed generic name for 873140. It was in-licensed for development from Ono Pharmaceutical Co., Ltd. in December 2002. 640385 was co-discovered with Vertex Pharmaceuticals, Inc, the GSK release added.
GlaxoSmithKline is one of the world's leading pharmaceutical and healthcare companies The company is a leader in HIV/AIDS treatments to patients and provides its anti-retrovirals to 64 of the least developed countries and Sub-Saharan Africa at not-for-profit prices.


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