This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The state of the vaginal epithelium affects the risk of HIV vaginal transmission. Human and monkey studies have shown that HIV or SIV vaginal transmission is decreased when estrogen is dominant. In past studies, we examined the efficacy of vaginal estriol cream in ovariectomized macaques against SIV vaginal transmission. Vaginal estriol applied twice weekly resulted in minimal serum estriol levels and had no effect on serum LH levels, which decline in the presence of systemic estrogen. Vaginal epithelia cornified and thickened in response to estriol therapy. Twelve macaques receiving vaginal estriol and eight placebo controls were challenged vaginally with SIVmac251. One of 12 estriol treated became infected, while six of eight controls became infected (p=0.0044). These data demonstrated that topical vaginal estriol strongly protects against SIV vaginal transmission, while having no detectable systemic effect. These results support the study of topical vaginal estriol in preventing HIV vaginal transmission in at-risk women. The earlier experiments have led to the current study in which ovary-intact female macaques will be challenged with SIVmac251 after topical estrogen cream treatment. The ultimate goal of this project is to show efficacy in females with normal menstrual cycles. Twelve normal female Rhesus macaques were assigned. Two groups of six each were treated with placebo cream or estriol cream to establish the optimum treatment schedule. Twice weekly treatments were begun in May of 2005, but was interrupted in August of 2005 by hurricane Katrina. The treatment was started again in October of 2005. The changes in vaginal epithelium were monitored by colposcopy. Treatment was changed to three times per week to increase the effect of the drug. Significant increases were seen in vaginal epithelial thickness. Animals will receive treatment until the optimal treatment schedules can be identified. All will be challenged by the vaginal route with SIVmac251.
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