Topical estrogen protects against SIV vaginal transmission without evidence of systemic effect.
BACKGROUND
Accumulating data suggest that the state of the vaginal epithelium affects a woman's risk of HIV vaginal transmission and several human and non-human primate studies have shown that the rate of HIV or SIV vaginal transmission is decreased when estrogen is dominant. Systemic estrogen can protect against SIV vaginal transmission.


OBJECTIVE
To determine the safety and efficacy of topical estrogen in preventing SIV vaginal transmission.


METHODS
The non-human primate model of HIV vaginal transmission was used to assess vaginal estriol cream in ovariectomized macaques.


METHODS
Twelve macaques were treated intravaginally with estriol and eight with placebo cream twice a week. The vaginal and systemic effects of estriol were determined by colposcopy and serum luteinizing hormone, levels of which would decline in the presence of systemic estrogen. After 5 weeks of therapy, the animals were challenged vaginally with pathogenic SIVmac251.


RESULTS
Vaginal estriol resulted in minimal serum estriol levels and had no effect on serum luteinizing hormone levels. Vaginal epithelia cornified and thickened significantly in response to estriol therapy. One of the estriol-treated animals became infected after this single challenge, while six of the control animals became infected (P = 0.0044).


CONCLUSIONS
These data demonstrate that topical vaginal estriol can strongly protect 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.
Smith
Stephen M
SM
Saint Michael's Medical Center and the New Jersey Medical School, Newark, New Jersey 07102, USA.
Mefford
Megan
M
Sodora
Donald
D
Klase
Zachary
Z
Singh
Mahender
M
Alexander
Nancy
N
Hess
David
D
Marx
Preston A
PA
D000287:Administration, Topical; D000818:Animals; D000914:Antibodies, Viral / Q000032:analysis; D018791:CD4 Lymphocyte Count; D003127:Colposcopy / Q000379:methods; D018562:Disease Transmission, Infectious / Q000517:prevention & control*; D004848:Epithelium / Q000187:drug effects; D004958:Estradiol / Q000097:blood; D004964:Estriol / Q000008:administration & dosage* / Q000097:blood; D005260:Female; D007986:Luteinizing Hormone / Q000097:blood; D008253:Macaca mulatta; D010052:Ovariectomy; D012313:RNA / Q000097:blood; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000635:transmission*; D014621:Vagina / Q000187:drug effects
D000914:Antibodies, Viral; D004958:Estradiol; D012313:RNA; D007986:Luteinizing Hormone; D004964:Estriol