Cervical Secretions from Women After Depot Medroxyprogesterone Acetate (Depo-Provera) Administration Promote HIV Infectivity Ex Vivo

Abstract

Depot medroxyprogesterone acetate (Depo-Provera) has been associated with an increased risk of HIV acquisition. We have previously shown that Depo-Provera administration increases immune markers for HIV preference on peripheral and cervical CD4⁺ T cells but decreases the levels of most immune mediators at vaginal and cervical mucosa. In this study, we determined the effect of cervicovaginal secretions from women before (visit 1), one month (visit 2) and three months (visit 3) after Depo-Provera treatment on HIV infectivity ex vivo. The effect of supernatants from vaginal, endocervical, and rectal swabs and from cervical cytobrush on HIV infectivity were assessed by a single-cycle infection assay using CCR5-using HIV-luciferase reporter viruses. We found that endocervical secretions from women after Depo-Provera treatment promoted HIV infectivity. When analyzing the association between endocervical mediator changes in response to Depo-Provera, available in our previous study, and the changes in HIV infectivity pre- and post-treatment, we found that changes in IL-17 and VEGF were positively associated with changes in HIV infectivity at visit 2 compared with visit 1, whereas changes in RANTES and IL-4 were negatively associated with HIV infectivity. The negative association between RANTES and HIV infectivity was also observed at visit 3 compared with visit 1. Additionally, changes in IL-1α at visit 3 were positively associated with changes in HIV infectivity compared with visit 1. These findings suggest that Depo-Provera may increase the HIV risk by shifting the mucosal milieu that promotes HIV infectivity.

Keywords: Depo-Provera; HIV infectivity; vaginal and cervical mucosa.

Figure 1

Vaginal and endocervical secretions from Depo-Provera treated patients enhance HIV infectivity. Vaginal, endocervical, and rectal secretions from swabs, and supernatants from the cytobrush were incubated with serum-free HIV-luc (JR-FL) for 1 h at 37 °C. Following incubation, samples were used directly to infect HeLa-CD4-CCR5 cells for 2 h at 37 °C. Following infection, cells were washed to remove unattached virus, and the level of HIV infection was determined 2 days later by luciferase assay. Luciferase values were normalized to virus incubated with PBS alone (untreated virus). Each dot represents an individual donor (median, IQR). A Wilcoxon matched-pairs signed-rank test was used for analysis. p ≤ 0.05 was considered significant. ns, not significant.