P40.10
Background: Heterosexual transmission accounts for the majority of new HIV infections with women being more likely than men to be infected during vaginal intercourse. Multiple soluble immune mediators in the female reproductive tract (FRT) that are hormonally regulated are protective against HIV. It is unclear as to whether loss of estradiol in postmenopausal women results in a blunted innate immune response in the FRT thereby making them more susceptible to acquiring and transmitting HIV. Furthermore, it is unknown whether postmenopausal women on hormone replacement therapy (HRT) might recover these innate immune functions. In this study, we investigated changes in soluble immune mediators, IL-6, TNF-a, IL-8, MIP3a, Elafin, SLPI and Human beta defensin-2 (HBD-2) in cervical-vaginal lavage (CVL) of HIV(+) and HIV(-) postmenopausal women compared to premenopausal women and women on HRT.
Methods: CVL from HIV(+) and HIV(-) premenopausal, postmenopausal and women on HRT were obtained from the Washington DC Women's Interagency HIV Study (WIHS) local repository and analyzed using commercially available ELISA. None of the HIV(+) women were on HAART. Statistical analyses were performed using the Kruskal-Wallis test (Graphpad Prism).
Results: HIV(+) postmenopausal women had significantly higher plasma viral load and lower CD4 counts compared to premenopausal women. We also observed significantly lower levels of HBD2 and MIP3a in postmenopausal women, from both HIV(+) and HIV(-) groups. In HIV(-) postmenopausal women and women on HRT, significant decreases in levels of TNF-a, IL-6, and anti-HIV protective factor SLPI was observed. However, both TNF-a and IL-6 were increased in HIV(+) postmenopausal women.
Conclusions: Our data indicate that both HIV status and menopausal status can dysregulate levels of soluble immune mediators in the FRT. A shift in the balance between proinflammatory factors and anti-HIV protective factors can result in higher susceptibility to acquisition and transmission of HIV in these women.
