Estrogen protects against vaginal transmission of simian immunodeficiency virus

Abstract

Postmenopausal women and women who use injectable, progestin-based contraceptives are at increased risk of human immunodeficiency virus (HIV) infection, suggesting that progesterone and estrogen affect HIV-1 vaginal transmission. To evaluate the individual roles of these sex hormones in vaginal transmission, ovariectomized female macaques were treated with either progesterone or estrogen followed by intravaginal inoculation with SIVmac. All 6 untreated control macaques and 5 (83%) of 6 progesterone-treated animals became infected following intravaginal SIV inoculation. Conversely, none of 6 estrogen-treated macaques was infected. Vaginal subepithelial inoculation of estrogen-treated animals resulted in infection, which shows that the block occurred at the vaginal epithelium and/or lumen. These data suggest that estrogen-deficient women are at increased risk of HIV infection, because their vaginal microenvironments are rendered more susceptible. Moreover, topical vaginal estrogen therapy may be an effective means of reducing HIV vaginal transmission in these high-risk groups. The World Health Organization estimates that 14.8 million women are living with human immunodeficiency virus (HIV) type 1 infection and that another 6.2 million women have died of AIDS [1]. Unprotected vaginal intercourse is the most common route through which women are infected with HIV-1 [2]. In sexually active women, the levels of estrogen and progesterone vary significantly under different natural and therapeutic conditions [3]. During the monthly reproductive cycle, estrogen levels steadily rise during the follicular phase and then fall after ovulation during the luteal phase, at which time progesterone levels rise. Women with low circulating levels of estrogen secondary to natural menopause or to therapy with depo-medroxy