Purpose: To assess the safety and acceptability of vaginal use of 0.1% and 0.25% UC-781 gel in sexually active HIV-uninfected women, and their male partners, and sexually abstinent HIV-infected women
Design: Single-center, phase I randomized, double-blind, controlled trial with 14 days of twice-daily product or control gel exposure
Study population: Sexually active, HIV-uninfected women at low-risk for HIV and their male partners; sexually-abstinent HIV-infected women; all age 18-45
Size: 36 sexually active HIV-uninfected women and up to 36 of their male partners; 18 sexually abstinent HIV-infected women
Treatment regimen:
Stage 1: HIV-uninfected, sexually active women and 1 male partner per woman:
12 women assigned to 0.1% UC-781 twice daily x 14 days; 12 women assigned to 0.25% UC-781 twice daily x 14 days; 12 women assigned to control gel twice daily X 14 days.
Stage 2: HIV-infected, abstinent women: 12 assigned to 0.25% UC-781 twice daily x 14 days; 6 assigned to control gel twice daily x 14 days
Study duration: Participant accrual will take 6 months. Each participant will be followed for 14 days in Stage 1 and 21 days in Stage 2. Total study duration will be 9 months.
Study Site: The Hope Clinic of Emory University, Decatur, GA
Primary Objectives:
* To assess the safety and toxicity of 0.1% UC-781 gel and 0.25% UC-781 gel administered intravaginally twice-daily for 14 days on the vulvar and cervicovaginal mucosa of sexually active HIV-uninfected women
* To assess the safety and toxicity of 0.25% UC-781 gel administered intravaginally twice-daily for 14 days on the vulvar and cervicovaginal mucosa of sexually abstinent HIV-infected women
Secondary Objectives:
* To assess the acceptability of 0.1% and 0.25% UC-781 gel administered intravaginally twice-daily for 14 days among HIV-uninfected, and the acceptability of 0.25% gel similarly administered to HIV-infected women
* To assess the effect of study product on vaginal microflora of HIV-uninfected and HIV-infected women
* To assess the systemic absorption of 0.1% and 0.25% UC-781 gel when administered intravaginally
* To assess HIV viral load in genital secretions in HIV-infected women during 0.25% UC-781 gel use
* To assess the genotypic resistance patterns of HIV in genital secretions and peripheral blood in HIV-infected women during 0.25% UC-781 gel use
* To assess the acceptability of 0.1% and 0.25% UC-781 gel in male sexual partners of HIV-uninfected women
Primary Endpoints:
The safety and toxicity of 0.1% UC-781 gel and 0.25% UC-781 gel administered intravaginally twice-daily for 14 days in sexually-active HIV-uninfected women and 0.25% UC-781 gel administered in sexually-abstinent HIV-infected women will be assessed by:
* Macroscopic and/or microscopic evidence of vulvar and/or vaginal epithelium damage, including ulceration, abrasion, severe erythema, and/or severe edema
* Macroscopic and/or microscopic evidence of cervical mucosal damage including ulceration, abrasion, severe erythema, and/or severe edema
* Symptoms of genital irritation, including burning, itching or soreness
* Laboratory evidence of grade 3 or higher toxicity for hematology, liver or renal function which cannot be attributed to another cause
Secondary Endpoints:
Acceptability of 0.1% and 0.25% UC-781 gel use by HIV-uninfected and 0.25% UC-781 gel use by HIV-infected women will be assessed by:
* Proportion of participants who at Day 14 visit indicate they would be 'somewhat unlikely' or 'very unlikely' to use 0.1% and 0.25% UC-781 gel during sexual intercourse in the future compared to control gel users
* Reported positive aspects of using 0.1% and 0.25% UC-781 gel compared to control gel users
* Reported negative aspects of using 0.1% and 0.25% UC-781 gel compared to control gel users
