Blocking α 4 β 7 integrin delays viral rebound in SHIV SF162P3 -infected macaques treated with anti-HIV broadly neutralizing antibodies.

Anti-HIV broadly neutralizing antibodies (bNAbs) may favor development of antiviral immunity by engaging the immune system during immunotherapy. Targeting integrin α ₄ β ₇ with an anti-α ₄ β ₇ monoclonal antibody (Rh-α ₄ β ₇ ) affects immune responses in SIV/SHIV-infected macaques. To explore the therapeutic potential of combining bNAbs with α ₄ β ₇ integrin blockade, SHIV _SF162P3 -infected, viremic rhesus macaques were treated with bNAbs only (VRC07-523LS and PGT128 anti-HIV antibodies) or a combination of bNAbs and Rh-α ₄ β ₇ or were left untreated as a control. Treatment with bNAbs alone decreased viremia below 200 copies/ml in all macaques, but seven of eight macaques (87.5%) in the bNAbs-only group rebounded within a median of 3 weeks (95% CI: 2 to 9). In contrast, three of six macaques treated with a combination of Rh-α ₄ β ₇ and bNAbs (50%) maintained a viremia below 200 copies/ml until the end of the follow-up period; viremia in the other three macaques rebounded within a median of 6 weeks (95% CI: 5 to 11). Thus, there was a modest delay in viral rebound in the macaques treated with the combination antibody therapy compared to bNAbs alone. Our study suggests that α ₄ β ₇ integrin blockade may prolong virologic control by bNAbs in SHIV _SF162P3 -infected macaques.
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