Antiretroviral therapy (ART) effectively suppresses HIV replication; however, lifelong treatment is associated with toxicity and, once ART is withdrawn, the virus rebounds. Persistent viral reservoirs form rapidly during acute HIV infection owing to high levels of viral replication in gastrointestinal tissues (GITs) and severe depletion of local CD4+ T cells. Here, Byrareddy et al. develop a recombinant monoclonal antibody against the α4β7 integrin, which is expressed on CD4+ T cells and is involved in their trafficking to GITs. Infusion of the antibody into SIV-infected macaques that had been treated with ART for 90 days led to persistent undetectable viral loads and normal CD4+ T cell counts.