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

Abstract

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, HSV-2 and HPV in vitro and in animal models. Design Phase 1, randomized, double-blind, placebo-controlled study in 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 (AE). Changes in vaginal flora were determined from Gram-stained vaginal smears and quantitative vaginal culture. Results No serious AEs or withdrawals due to AEs were reported. Genitourinary symptoms were reported as follows: VivaGel (n=17/22; 77.3%), VivaGel placebo (n=14/21; 66.7%) and HEC (n=8/18; 44.4%) (NS, p=0.1). The incidence of abnormal pelvic exam findings was similar across all gel arms of the study. Using pair-wise comparison, women in the VivaGel arm had a significantly higher incidence of related genitourinary AEs 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. Conclusions VivaGel was generally well tolerated and comparable with the VivaGel placebo, although there was a higher incidence of low grade related genital AEs compared to the HEC placebo gel.

Nuclear Receptor Signaling Inhibits HIV-1 Replication in Macrophages through Multipletrans-Repression Mechanisms

“…Over the past decade, a great deal of effort has been devoted to developing anti-HIV microbicides that can effectively prevent virus transmission (35,76,85,102,154). With the exception of the CAPRISA 004 trial (2), most microbicide trials conducted to date have failed due to a number of factors, including poor adherence (141) and unexpected inflammation that increased the risk of transmission (1,(39)(40)(41)(148)(149)(150).…”

Antiretroviral Therapy through Barriers: A Prominent Role for Nanotechnology in HIV-1 Eradication from Sanctuaries

“…It has been recently demonstrated that HIV-1 exposure actively increases P-gp expression in bowel mucosa, decreasing the concentration of orally administered ARVs within the gut-associated lymphoid tissue [41]. In this context, it has been demonstrated that P-gp is overexpressed in the cervico-vaginal mucosa as well, which is the target of some recent studies on HIV-1 sexual transmission [42,43]. Indeed, various pharmacological formulations of ARVs have been tested vaginally or orally for a pre-exposure prophylaxis of HIV-1 in women, but the presence of P-gp significantly diminishes the efficacy of the administered ARV [43].…”

“…In this context, it has been demonstrated that P-gp is overexpressed in the cervico-vaginal mucosa as well, which is the target of some recent studies on HIV-1 sexual transmission [42,43]. Indeed, various pharmacological formulations of ARVs have been tested vaginally or orally for a pre-exposure prophylaxis of HIV-1 in women, but the presence of P-gp significantly diminishes the efficacy of the administered ARV [43]. Finally, P-gp can be highly overexpressed in response to therapy administration, as well documented by studies on CD8+ T lymphocytes isolated from the peripheral blood of HIV-1-infected patients under ARV treatment [44].…”

Young Women's Experience with Using Videoconferencing for the Assessment of Sexual Behavior and Microbicide Use

“…Participants were young women who participated in two parallel and interlocked studies: a placebo-controlled Phase 1 microbicide safety and acceptability study and a simultaneous study exploring microbicide acceptability and participants' attitudes about it (for details, see McGowan et al, 36 Carballo-Diéguez et al, 37 and Giguere et al…”