An HIVgp41 vaccine protects CD4 central memory T cells in SHIV-infected macaques

► We model a therapeutic vaccine based on a specific 3S/gp41 HIV motif against AIDS in macaques. ► We show that 3S vaccination preserved the CD4+ central memory T cells in infected-animals. ► We show that 3S antibodies limit side effects in infected-animals. ► We provide a framework for understanding protection against CD4+ T cell depletion ► Our findings suggest that an anti-3S therapeutic vaccine strategy might afford protective efficacy against AIDS pathogenesis.