Topical microbicides represent an emerging strategy for the prevention of transmission of HIV and other sexually transmitted infections. A successful topical microbicide product will be applied prior to intercourse, without necessitating partner consent, and will be active against a variety of STIs, including HIV. It will be acceptable to potential users in terms of physical characteristics, availability, ease of use, safety and efficacy properties. We have utilized the macaque vaginal safety model (currently contracted by the NIH, N01-AI-95388) to provide standardized preclinical safety data for numerous topical microbicide products in development. In this model, measures of product safety include cervicovaginal colposcopy, vaginal microbiologic evaluation, and vaginal pH monitoring. This model characterizes the vaginal environment's response to repeated topical product applications in the absence of the exogenous factors of intercourse and potentially infectious ejaculate. While our preclinical evaluations of topical microbicide products have been well-rounded in many aspects, we have yet to investigate the effects of sexual intercourse on the cervicovaginal environment. Mucosal perturbation and potential micro-trauma in the form of epithelial abrasions are likely to result from sexual activity. Additionally, the effects that seminal fluid may induce on the cervicovaginal environment, as well as its effects vis-?-vis topical microbicide product safety and efficacy, have not yet received their due attention. We propose to enhance our standardized vaginal safety evaluations conducted in the pigtailed macaque model to include evaluations after sexual activity and with the presence of seminal fluid. With continued R33 funding, we will collect baseline data from 24 female macaques assessing the cervicovaginal environment before and after mating. In addition, we will collect parallel assessments, when mating has occurred with a placebo gel (HEC universal placebo) in place. These studies will provide urgently needed data regarding topical microbicide use with coital activity. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21AI071939-02
Application #
7501456
Study Section
Special Emphasis Panel (ZAI1-RB-A (M1))
Program Officer
Turpin, Jim A
Project Start
2007-09-30
Project End
2009-08-31
Budget Start
2008-09-01
Budget End
2009-08-31
Support Year
2
Fiscal Year
2008
Total Cost
$269,419
Indirect Cost
Name
University of Washington
Department
Obstetrics & Gynecology
Type
Schools of Medicine
DUNS #
605799469
City
Seattle
State
WA
Country
United States
Zip Code
98195
Sweeney, Yvonne T Cosgrove; Angeles, Ray O; Cummings, Peter K et al. (2011) Pigtailed macaque model refinement: topical microbicide safety in the presence of coitus. J Med Primatol 40:327-34