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. Background: HIV continues to be a growing epidemic despite various efforts to prevent and treat this disease. Potential methods of prevention include microbicides, creams or gels that can be used by women inside the vagina to protect them from acquiring infections during sexual intercourse. Microbicides are being developed however, the methods to test safety are not sensitive enough. In studies of two potential microbicides, the scientists found that the women who used the medications were more susceptible to HIV than those who did not. Early animal and human studies did not predict safety in these drugs therefore more sensitive methods are needed. Optical coherence tomography (OCT) holds promise as a high resolution, non-invasive method to evaluate the lining (epithelium) of the vagina and cervix. In animal studies, it can detect epithelial changes not detected by colposcopy, the current gold standard for safety evaluation in humans. Hypotheses: Hypothesis 1: In the study dosing, N-9 will provide minimal, if any, changes in the cervicovaginal epithelium. Hypothesis 2: OCT will detect minor changes in the cervicovaginal epithelium not detected by colposcopy.
Specific Aims and Procedures (summary): The primary aim of the study is to evaluate whether regular use of an over-the-counter formulation of N-9 will result in epithelial toxicity detectable by OCT but not by colposcopy. Volunteers will be randomized to use either an over-the-counter spermicide, Nonoxynol-9 (Conceptrol ) or placebo gel (Hydroxyethylcellulose - HEC, a constituent in over-the-counter vaginal medications) intravaginally twice daily for 5.5 days. After the initial screening visit, women will be evaluated by OCT and colposcopy at Visit 1 (day 0), Visit 2 (day 6) and Visit 3 (day 13). Before and after treatment, OCT and colposcopy findings will be compared. The secondary aim of the study is to describe women's motivation and barriers to potential participation in a vaginal product safety study and to understand women's perceptions of the OCT and colposcopy experience. This secondary aim is hypothesis-generating and therefore no planned hypotheses are put forth. A series of open-ended questions over the course of three audio-recorded semi-structured interviews will address the topics of motivations, barriers, and perceptions. The analytic plan for these qualitative data will enable themes to be identified and summarized for each topic. Experimental Design (summary): Reproductive-aged (18-45 years) women will be targeted for enrollment in this study. They will be recruited with the use of flyers and study announcements on the UTMB daily announcements, and by word of mouth. They will have a telephone screening call in which questions about medical history will be asked. Women who are eligible will be screened for sexually transmitted diseases, cervical dysplasia and cancer, and pregnancy. Up to twenty-five women will be screened to enroll 18 women in the study;we anticipate that some will become ineligible because of their screening test results. Eighteen women will have an initial visit in which OCT and colposcopy will be performed. The participant will then receive either placebo (HEC) or Nonoxynol-9 to be used intra-vaginally twice daily for 5.5 days. The participant will return the day of the last dose for a repeat OCT and colposcopy genital examination. She will return a week later for OCT and colposcopy genital examination after a week without medication. She will be asked to be abstinent and to use no other products in the vagina during the course of the study. At each visit, she will also participate in an interview to explore her experience with being involved in the study, using the vaginal gel product, and undergoing the examination with OCT and colposcopy. Significance (summary): New methods of detection of epithelial changes after use of vaginal microbicides are needed in order to ensure the safety of these products. If OCT is determined to detect changes not noted on colposcopy, as we have seen in animal studies, it has great potential to enhance our ability to develop safe vaginal medications for the prevention of HIV and potentially help to slow the rate of acquisition of this disease.
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