Abstract: Innate immune activation was a strong predictor of HIV acquisition in women at risk for HIV in CAPRISA 004. Identifying the cause(s) of activation could enable targeted prevention interventions. In this study, plasma concentrations of lipopolysaccharide, soluble CD14, and intestinal fatty acid–binding protein did not differ between subjects who did or did not subsequently acquire HIV nor were these levels correlated with plasma cytokines or natural killer cell activation. There was no difference between HIV acquirers and non-acquirers in the chemokine and cytokine responses of peripheral blood mononuclear cells stimulated with TLR2, 4, or 7/8 agonists. Further studies are required.