Expanded Phase I safety and acceptability study of 6% cellulose sulfate vaginal gel

ArticleinAIDS 19(18):2157-63 · January 2006with9 Reads
DOI: 10.1097/01.aids.0000194797.59046.8f · Source: PubMed
Abstract
An expanded Phase I trial was performed to assess the safety and acceptability of 6% cellulose sulfate gel (CS) in comparison with K-Y Jelly. Sexually abstinent (cohort I) and sexually active (cohort II) women in India, Nigeria and Uganda applied 3.5 ml of either 6% CS gel or K-Y Jelly for seven consecutive days. Safety was assessed by symptoms and signs (including colposcopy) of genital irritation, review of adverse events, and by changes in vaginal health as assessed by microscopy. One hundred and eighty women (90 on CS and 90 on K-Y Jelly) were enrolled. Baseline characteristics of women in both gel groups were similar. In cohort I, six (14%) women on CS and 12 (27%) on K-Y Jelly reported genital symptoms, two (in K-Y Jelly group) of whom withdrew from the study. New colposcopy findings or findings showing deterioration were detected in four (9%) women on CS and nine (21%) women on K-Y Jelly in cohort I. Two women on CS and three on K-Y Jelly in cohort II reported genital symptoms. Five women (11%) in each gel group in cohort II had new colposcopy findings or findings showing deterioration. The differences between the gel groups were not statistically significant. The majority of women had no problem with their assigned product. A vaginal application of 6% cellulose sulfate twice daily for seven consecutive days is as safe and well tolerated as a similar regimen of K-Y Jelly. Further development of 6% CS for prevention of HIV and pregnancy is recommended.
    • "Although microbicides are used by women, gender norms will still influence how and when women use microbicides. Evidence to date shows that women and men in the Americas tend toward prioritizing the need for microbicides that would be " unnoticeable " during sex[60,184185186187188189. Studies in Thailand and India have focused on whether or not it would be feasible to use a microbicide without a partner noticing it, with seven studies (two from India, four from Thailand, and one from both) tending toward use without partner's knowledge not being feasible[30,62,90,102,103,184,190,191]and five studies (two from India and three from Thailand) tending toward it being feasible[103,139,192193194. In a few studies, a motivation to discuss use with stable partners was driven by a desire to avoid accusations of infidelity if the partner noticed the gel during sex[30,139,191,193]. "
    Chapter · Oct 2014 · Virology Journal
    • "In these settings, new, female-initiated HIV prevention agents are potentially very appealing to both women at risk and to public authorities responsible for prevention. Apart from some limited trials of earlier candidate microbicides in two sites in Thailand6263646566 and India66676869707172, virtually all of the recent trials of microbicides have been conducted in African countries. Asia-Pacific countries have been considered to have HIV incidence that is too low to justify efficacy trials, but high enough in some areas for microbicides to play an important role in prevention once they are proven safe and efficacious. "
    [Show abstract] [Hide abstract] ABSTRACT: Background The acceptability of female-controlled biomedical prevention technologies has not been established in Papua New Guinea, the only country in the Pacific region experiencing a generalised, moderate-prevalence HIV epidemic. Socio-cultural factors likely to impact on future product uptake and effectiveness, such as women’s ability to negotiate safer sexual choices, and intravaginal hygiene and menstrual practices (IVP), remain unclear in this setting. Methods A mixed-method qualitative study was conducted among women and men attending a sexual health clinic in Port Moresby. During in-depth interviews, participants used copies of a hand-drawn template to indicate how they wash/clean the vulva and/or vagina. Interviewers pre-filled commercially available vaginal applicators with 2-3mL KY Jelly® to create a surrogate vaginal microbicide product, which was demonstrated to study participants. Results A total of 28 IDIs were conducted (women=16; men=12). A diverse range of IVP were reported. The majority of women described washing the vulva only with soap and water as part of their daily routine; in preparation for sex; and following sexual intercourse. Several women described cleaning inside the vagina using fingers and soap at these same times. Others reported cleaning inside the vagina using a hose connected to a tap; using vaginal inserts, such as crushed garlic; customary menstrual ‘steaming’ practices; and the use of material fragments, cloth and newspaper to absorb menstrual blood. Unprotected sex during menstruation was common. The majority of both women and men said that they would use a vaginal microbicide gel for HIV/STI protection, should a safe and effective product become available. Microbicide use was considered most appropriate in ‘high-risk’ situations, such as sex with non-regular, transactional or commercial partners. Most women felt confident that they would be able to negotiate vaginal microbicide use with male sexual partners but if necessary would be prepared to use product covertly. Conclusions Notional acceptability of a vaginal microbicide gel for HIV/STI prevention was high among both women and men. IVP were diverse in nature, socio-cultural dimensions and motivators. These factors are likely to impact on the future acceptability and uptake of vaginal microbicides and other biomedical HIV prevention technologies in this setting.
    Full-text · Article · Nov 2012
    • "CS, which was formulated into a microbicide known as Ushercell, was shown in vitro to have broad activity against HIV-1, herpes simplex virus types 1 and 2, Neisseria gonorrhoeae, and Chlamydia trachomatis [14]. After numerous clinical trials that established the safety of Ushercell151617181920, two separate phase III trials were initiated to assess its efficacy against HIV-1 transmission. Both trials were halted when, in one trial, an increased prevalence of HIV-1 infection was detected among women using Ushercell [21] . "
    [Show abstract] [Hide abstract] ABSTRACT: Continued efforts are being directed toward the development of microbicides that will be used to reduce or eliminate the risk of HIV-1 sexual transmission. Unfortunately, clinical trials involving polyanion-containing microbicide formulations, including Carraguard (λ-carrageenan [LC]) and Ushercell (cellulose sulfate [CS]) demonstrated that these products were ineffective and may have, in some circumstances, increased the risk of HIV-1 infection. These findings prompted reassessments of the in vitro activities of these agents to determine whether variables that can affect agent safety and efficacy had been overlooked during preclinical testing. One such variable is product retention and loss following topical application. In the present studies involving an HIV-1-susceptible cell line and primary human immune cells, product loss was mimicked by introducing and then removing polyanionic compounds prior to HIV-1 infection. In these in vitro "washout" experiments, LC and CS significantly enhanced HIV-1 infection, despite potent antiviral activity when introduced simultaneously with the virus. The presence and magnitude of this effect were dependent on compound identity and concentration; target cell; interval between compound removal and virus challenge; and coreceptor usage. Levels of enhancement (relative to controls) were considerable, exceeding a 200% increase (CS) in P4-R5 MAGI cells and a 300% increase (LC) in human peripheral blood mononuclear cells. These studies, which demonstrate significant increases in HIV-1 infection subsequent to application and removal of LC and CS, support plausible explanations for the failures of microbicides formulated from these compounds. Detailed studies are now underway to determine the mechanism responsible for this enhancement effect and to assess the potential contribution of this effect to the clinical failures of these agents.
    Full-text · Article · Jan 2012
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