Estrogen Protects against Vaginal Transmission of SIV

S. SMITH^1‚2, P. CHARKRABORTY¹, G. BASKIN³, and P. MARX*^3‚4. ¹Saint Michael's Med. Ctr. and ²Univ. Med. and Dent. of New Jersey, Newark, NJ; ³Tulane Regional Primate Res. Ctr., Tulane Univ. Med. Ctr., Covington, LA; and ⁴Aaron Diamond AIDS Res. Ctr., Rockefeller Univ., New York, NY

To assess the individual effects of estrogen and progesterone on SIV vaginal transmission and also to model HIV vaginal transmission in post-menopausal women, we studied ovariectomized macaques. 18 animals underwent bilateral ovariectomy. Subsequently, six animals received a progesterone implant; six animals received estrogen implants; and six animals received no implant. Hormone levels reached the expected values in each group. The untreated, ovariectomized animals did not have significant amounts either progesterone or estrogen; the estrogen treated animals had follicular phase levels of estrogen (avg. 399 pg/ml) and no detectable progesterone; the progesterone treated animals had luteal levels of progesterone (avg. 4.5 ng/ml) and no appreciable estrogen. Animals were then challenged intravaginally with SIVmac251 (640TCID₅₀) and studied serially to establish the presence or absence of infection. Virus was isolated from 5/6 progesterone treated animals and 6/6 untreated animals at both Days 14 and 42 post-challenge. Virus was not isolated from any of the estrogen treated animals at Days 14, 42, or 308. Accordingly, none of the estrogen treated animal seroconverted to SIV and none had detectable SIV proviral DNA in their PBMCs as determined by nested PCR.  In summary, 5/6 progesterone treated and 6/6 untreated animals became infected after intravaginal challenge, while none of the estrogen treated animals became infected. The progesterone and untreated animals had thinned vaginal epithelia (avg. 4 microns), while the estrogen treated animals had much thicker vaginal epithelia (avg. 240 microns). Vaginal epithelial thickness, as seen in our prior study, inversely correlated with susceptibility to infection. These data suggest:
1. Women with thin vaginal epithelia, such as post-menopausal women, may be more susceptible to HIV-1 vaginal transmission;
2. Estrogen therapy may reduce this increased susceptibility.

Key Words: Estrogen, Transmission, Vaginal

© 7th Conference on Retroviruses and Opportunistic Infections,
Foundation for Retrovirology and Human Health