Evaluation of an antibody to α₄β₇ in the control of SIVmac239-<i>nef-stop</i> infection.

Abstract

Treatment of SIV-infected rhesus macaques with short-term antiretroviral therapy (ART) and partially overlapping infusions of antibody to integrin α₄β₇ was reported to induce durable posttreatment viral suppression. In an attempt to replicate those observations, we treated macaques infected with the same virus and with the same ART and monoclonal antibody (mAb) regimens (anti-α₄β₇ versus control mAb). Sequencing demonstrated that the virus used was actually SIVmac239-<i>nef-stop</i>, not wild-type SIVmac239. A positive correlation was found at 2 weeks after infection between the frequency of repair of attenuated <i>Nef-STOP</i> virus to pathogenic <i>Nef-OPEN</i> and plasma SIV RNA levels. Levels of plasma viremia before the first antibody infusion and preinfection levels of α₄β₇ ^hi CD4⁺ T cells, but not treatment with antibody to α₄β₇ , correlated with levels of viral replication upon discontinuation of all treatments. Follow-up plasma viremia, peripheral blood CD4⁺ T cell counts, and lymph node and rectal tissue viral load were not significantly different between anti-α₄β₇ and control mAb groups.