Phase 1 randomized trial of the vaginal safety and acceptability of SPL7013 gel (VivaGel) in sexually active young women (MTN-004)

Objectives: The study was designed to assess the safety, adherence, acceptability, and effect on vaginal microflora of 3% SPL7013 Gel (VivaGel), a novel dendrimer topical microbicide that inhibits HIV, herpes simplex virus-2, and human papillomavirus in vitro and in animal models. Design: Phase 1, randomized, double-blind, placebo-controlled study on sexually active women. Methods: Sixty-one sexually active women aged 18-24 years were recruited from three sites in the United States. Participants were randomized 1 : 1 : 1 to receive VivaGel, VivaGel placebo, or a hydroxyethylcellulose (HEC) placebo twice daily for 14 consecutive days. Safety endpoints included genitourinary and/or other adverse events. Changes in vaginal flora were determined from Gram-stained vaginal smears and quantitative vaginal culture. Results: No serious adverse events or withdrawals due to adverse events were reported. Genitourinary symptoms were reported as follows: VivaGel (n = 17/22; 77.3%), VivaGel placebo (n = 14/21; 66.7%), and HEC (n = eight of 18; 44.4%; not significant, P = 0.1). The incidence of abnormal pelvic examination findings was similar across all gel arms of the study. Using pairwise comparison, women in the VivaGel arm had a significantly higher incidence of related genitourinary adverse events compared with women in the HEC gel arm (0.297 versus 0.111 per 100 person-years, respectively; P = 0.003). Exposure to VivaGel and VivaGel placebo resulted in minor shifts in the vaginal microflora, but there was no overall impact on incidence of bacterial vaginosis as assessed by Nugent score. Conclusion: VivaGel was generally well tolerated and comparable with the VivaGel placebo, although there was a higher incidence of low-grade related genital adverse events compared to the HEC placebo gel. (C) 2011 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins