The baseline vaginal immune milieu is an important determinant of the inflammatory response induced by penile-vaginal sex.

Elevated cervicovaginal cytokines/chemokines and epithelial disruption are associated with HIV risk. While penile-vaginal sex induces transient cervicovaginal inflammation and epithelial disruption, there is considerable interindividual heterogeneity. We defined genital inflammation using a multi-cytokine score and hypothesized that sex-induced inflammation would depend on the pre-existing vaginal immune milieu. We quantified HIV-associated immune factors in cervicovaginal secretions of HIV-uninfected women before and 1 h after penile-vaginal sex. Cervicovaginal IgA and IgG increased after sex, and baseline IgA was associated with inflammatory cytokines and epithelial disruption. Post-sex vaginal immune factors strongly associated and clustered with pre-sex concentrations, and participants with baseline inflammation remained inflamed after sex. Sex induced greater relative changes in inflammatory cytokines and epithelial disruption among participants with lower baseline levels, but not in chemokines. In conclusion, the baseline vaginal milieu determines the inflammatory effects of sex; specifically, sex elicits a greater change in inflammatory responses in women with baseline vaginal immunoquiescence.