Glaxo Wellcome has reported that a chemically-modified chemokine,AOP-RANTES, can inhibit the entry of HIV-1 into lymphocytes and also macrophages. Recent research has demonstrated that HIV-1 utilises certain co-receptors such as CCR5 and CXCR4, in addition to CD4, to gain entry into host cells (see also page 23).
HIV uses the CCR5 receptor to gain entry into macrophages and lymphocytes during the initial stages of infection and the asymptomatic phase of the disease. Later on, mutant virus able to infect T cells via the CXCR4 receptor predominate, and this is associated with progression to symptomatic disease.
GW has been able to move forward quickly on these findings because it already has a chemokine program ongoing in asthma. Another modified version of RANTES, called Met-RANTES, has been shown to block migration of T cells, monocytes and eosinophils in models of inflammation, and GW is seeking to develop drugs with similar properties for clinical development.
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