Depo-Provera alters cervical immune responses and increases HIV infectivity ex vivo: a longitudinal study.

Abstract

Abstract Depo-Provera (Depot medroxyprogesterone acetate, MPA) is associated with an increased risk of HIV acquisition; however, its impact on the cervicovaginal immune milieu and HIV infectivity ex vivo is not well characterized. In a longitudinal study, we investigated the impact of Depo-Provera use by healthy women on levels of cervical immune mediators, expression of immune markers for HIV preference (CCR5, integrin a4b7, CD38) on cervical CD4+ T cells, and HIV infectivity ex vivo at baseline (visit 1), one month (visit 2) and three months (visit 3) after Depo-Provera treatment. Forty-seven healthy women who met the eligibility criteria were enrolled (median age 26, IQR 22.5–30). Cervical cytobrush cells and secretions from vaginal, endocervical, and rectal swabs were collected. Flow cytometry analysis indicated a significant increase in the frequency of cervical CCR5+CD4+T cells at visit 3 compared to visit 1. There was also an increasing trend in the frequency of cervical CD4+ cells expressing integrin a4b7 in response to Depo-Provera. Levels of several cytokines including G-CSF, GM-CSF, IL-6, MIP-1b, and VEGF in vaginal and cervical secretions were significantly decreased at visits 2 and 3 compared to visit 1. At visit 3, cervical levels of immune mediators remained suppressed despite a decreased serum concentration of MPA, suggesting a prolonged effect of Depo-Provera on mucosal immune responses. Cervicovaginal secretions from women after receiving Depo-Provera (visits 2 and 3) promoted HIV infectivity ex vivo compared to those at visit 1. Further studies on the modulation of mucosal immune responses and HIV transmission by Depo-Provera will offer insights into developing better strategies for HIV prevention.