The Use of alpha-4 beta-7 integrin Inhibitors to Inhibit HIV Transmission and Infection

Description:

This invention involves the use of inhibitors of alpha-4 beta-7 (a4b7) integrin to inhibit HIV transmission/infection, as a prophylactic to inhibit onset of the acute stage of HIV infection or to treat HIV infection. The a4b7 integrin inhibitors were previously developed for use in other diseases, such as multiple sclerosis or inflammatory bowel disease.

a4b7 integrin is a multifaceted target for HIV infection and recent studies indicate that it is important for establishing HIV infection through multiple paths. Studies indicate that: 1) CD4 T-cells present in vaginal and anal mucosa have high levels of a4b7 integrin, making CD4 T-cells permissive to HIV infection; 2) a4b7 integrin is important for cell to cell transmission of HIV; 3) a4b7 integrin is used to dysregulate the host humoral response to HIV; and 4) HIV acts on a4b7 integrin through an epitope in V2 loop of GP120, identified as important for HIV vaccine protection. Additionally, primate studies indicate that a4b7 integrin inhibition of HIV infection preserves gut-associated lymphoid tissue (GALT) generally destroyed during the acute phase of HIV infection.