While combination antiretroviral therapy (cART) has improved the clinical outcome for HIV-infected individuals, persistence of viral reservoirs in the peripheral blood and lymphoid tissues remains a hurdle to complete eradication of virus and cure of the infection. The concept that HIV preferentially infects discrete subsets of CD4+ T cells underscores the need to develop therapeutics that exploit specific cell-virus interactions. T cells expressing integrin alpha4beta7 not only regulate migration into the gutassociated lymphoid tissue (GALT), but also concomitantly bind HIV, placing them in a prime position to disseminate HIV throughout the tissue. Previously, it has been shown that the HIV envelope protein gp120 binds to alpha4beta7 on CD4+ T cells in vitro, alpha4beta7high CD4+ T cells are highly susceptible to productive HIV infection in vitro, and the administration of anti-alpha4beta7 monoclonal antibody (mAb) prevents and/or delays transmission of SIV upon repeated challenges and preserves CD4+ T cells in rhesus macaques. Furthermore, it has been demonstrated that administration of anti-alpha4beta7 mAb in SIV-infected rhesus macaques receiving cART suppresses plasma viremia for extended periods following discontinuation of cART, collectively suggesting that sustained virologic remission in the absence of cART may be achieved via direct targeting of alpha4beta7 integrin. It is well established that the vast majority of HIV-infected individuals treated with cART experience plasma viral rebound within weeks of cessation of therapy. Considering that current research on the treatment of HIV-infected individuals has been heavily focused on developing strategies aimed at achieving sustained virologic remission in the absence of cART, it is of great interest to investigate whether administration of anti-alpha4beta7 mAb can prevent plasma viral rebound and allow durable suppression of viral replication in HIV infected individuals after discontinuation of cART. We propose to examine the effect of vedolizumab, an FDA approved anti-alpha4beta7 mAb for the treatment of ulcerative colitis and Crohn s disease, on plasma viral rebound in HIV-infected individuals following analytical treatment interruption (ATI).