P25.01
Background: Cervicovaginal HIV shedding increases HIV transmission. Genital tract inflammation increases shedding through production of cytokines/chemokines which recruit and activate HIV target cells. We evaluated whether cervical immune mediators present before HIV acquisition affected later HIV shedding and whether after acquisition, levels of mediators differed between shedders and non-shedders.
Methods: We used cervical samples from 157 women with well-documented HIV seroconversions during the Hormonal Contraception and HIV (HC-HIV) study in Uganda and Zimbabwe. Samples were from the visit before (T-1), at (T0), and 2 visits after seroconversion (T+1 and T+2). We measured 8 biomarkers of inflammation and immunity (IL-1β, IL-1RA, IL-6, IL-8, RANTES, MIP-3α, VEGF, ICAM-1) by electrochemiluminescence multiplex and antibacterial proteins SLPI and BD-2 by ELISA. We used the Wilcoxon test and generalized linear models to evaluate the association between mediator levels and shedding, and other covariates' impact on shedding.
Results: The only immune mediator at T-1 associated with women who shed (vs. those who did not) at T0 (seroconversion) was RANTES (p=0.05). In both shedders and non-shedders, seroconversion was followed by a significant increase in RANTES and decrease in IL-8 and VEGF (T-1 vs T0). Among non-shedders only, IL-6 and BD-2 decreased and MIP-3α and ICAM-1 increased while, among shedders, SLPI decreased after seroconversion. The magnitude of changes in RANTES, SLPI and MIP-3α between T-1 and T0 was significantly greater in shedders vs. non shedders. At T0, shedders had lower levels of SLPI and MIP-3α than non-shedders. The difference remained significant at T+1 for MIP-3α.
Conclusions: Specific immune mediator profiles are associated with risk of HIV acquisition and cervical shedding. Increased RANTES and decreased SLPI were associated with increased risk of HIV shedding, possibly due to their effects on HIV target cells and innate immunity.
