Combined impact of recent sexual activity and vaginal product use on genital immune activation in South African women: implications for HIV risk.

Adolescent girls and young women (AGYW) in South Africa experience a disproportionate burden of HIV infection. Genital inflammation has been implicated in increased HIV susceptibility through enhanced availability of target immune cells; however, the effects of recent sexual activity and vaginal-stimulating product (VSP) use on mucosal immune responses remain incompletely defined. This study characterised mucosal immune profiles following recent sexual exposure and VSP use in adolescent and adult women. HIV-negative sexually active adolescents (14-19 years) and adult women (25-35 years) were enrolled in a longitudinal cohort in KwaZulu-Natal, South Africa. Cervical cytobrush samples and cervicovaginal secretions were collected at baseline (≥ 2 weeks abstinence) and following reported sexual activity and/or VSP use. Cervical T-cell activation markers (CD38, HLA-DR, CCR5, α4β7) were quantified by flow cytometry, and 18 cytokines and chemokines were measured using a multiplex assay. Associations with time since last sexual intercourse were assessed using correlation analyses, and factors associated with genital inflammation were evaluated using weighted logistic regression. Recent sexual activity showed inverse associations with several pro-inflammatory cytokines, including MIP-1α, IL-1α, IL-1β, GM-CSF, and IL-17, consistent with a transient pattern of mucosal immune activation following exposure. In multivariable models, recent sexual activity (OR 0.58; p = 0.009) and bacterial vaginosis (OR 2.38; p = 0.017) were independently associated with genital inflammation, whereas VSP use was not statistically significant after adjustment (OR 1.63; p = 0.187). Although higher cytokine concentrations were observed among VSP users in unadjusted analyses, including IL-1α in adolescents (p = 0.001) and MIP-1α in adults (p = 0.017), these associations did not remain significant after correction for multiple testing. Overall, these findings suggest that recent sexual activity is associated with transient changes in mucosal immune mediators, while VSP use does not independently predict genital inflammation in this cohort after adjustment for confounding and multiple testing. These results highlight the importance of timing of exposure in interpreting mucosal immune measurements and support further longitudinal studies with precise sampling intervals to better define post-coital immune dynamics and the role of behavioural practices in shaping genital immunity.