预防艾滋病毒性传播的杀微生物剂的研究现状

杀微生物剂的应用是预防艾滋病毒性传播的重要途径.本文阐明了艾滋病毒的性传播机制和杀微生物剂的作用机理,进一步综述了杀微生物剂的类型及其发展前景.     

Rheological properties of contraceptive gels

The rheological properties of 4 commercially available contraceptive drug delivery gels and their dilutions with a vaginal fluid simulant were measured. These properties govern the critical functions of spreading and retention of these gels over the vaginal surfaces. Measurements made on Conceptrol, KY Plus, Gynol II, and Advantage-S included stress growth, stress relaxation and residual stress, and the shear rate dependence of viscosity. All gels exhibited non-Newtonian behavior including shear thinning and viscoelasticity. Conceptrol and Gynol II had no residual stress, while both KY Plus and Advantage-S did. The gels differed in their response to dilution with vaginal fluid simulant.     

Single and multiple exposure tolerance study of polystyrene sulfonate gel: a phase I safety and colposcopy study

OBJECTIVES: To evaluate symptoms and signs of genital irritation, vaginal leakage and acceptability of polystyrene sulfonate (PSS), which is being studied as a vaginal contraceptive and microbicide. METHODS: Forty-nine women applied 2.5 mL of either 5% PSS, 10% PSS, PSS vehicle, or Conceptrol (a marketed spermicidal product containing 4% nonoxynol-9) for 6 consecutive days. RESULTS: All women completed the study except one in the Conceptrol group who experienced vaginal symptoms after her first use and was discontinued. After both the first use and after all uses, irritation was seen among more women in the Conceptrol group than in the PSS groups, reaching statistical significance with regard to any evidence of irritation, signs of irritation and product-related irritation. There were no adverse events that were serious, unexpected and related to product use in any group. The 5% concentration of PSS may be preferable in terms of leakage and acceptability. CONCLUSION: The results suggest that PSS has a safety profile comparable to that of the marketed nonoxynol-9 product, Conceptrol, and appears to be associated with less genital irritation.     

Male tolerance study of 1% C31G

BACKGROUND: C31G is being studied as a vaginal contraceptive and microbicide. This study was conducted to ensure that male partners of the women in future trials of C31G will not be subjected to an undue risk of penile irritation. METHODS: This was a randomized, double-blinded, single-center Phase I study in circumcised and uncircumcised men to assess penile irritation, safety and acceptability of seven consecutive daily doses of 1.0% C31G compared with a marketed spermicide, Extra Strength Gynol II(R) (3% nonoxynol-9) (ES Gynol II). Each participant was instructed to apply the study product to his penis at bedtime, to wash it off 6-10 h later, and to record any symptoms on a diary card. At the follow-up visit, a genital examination was performed and participants were again asked about adverse events and to complete an acceptability questionnaire. RESULTS: Of the 36 men enrolled, 12.5% of C31G users and 16.7% of Extra Strength Gynol II users reported product-related adverse events (AEs). All product-related AEs were considered mild by the investigator, except for one in the ES Gynol II group. Both products were acceptable. CONCLUSION: The manner in which the products were used in this study is not the route by which men will be exposed to such products in actual use, and results should be considered in this light. Based on the observations in this study, C31G appears to be at least as safe and acceptable for male penile exposure as the marketed product ES Gynol II.     

Recombinant Streptococcus gordonii for Mucosal Delivery of a scFv Microbicidal Antibody

The gram-positive bacterium Streptococcus gordonii was engineered to express the microbicidal molecule H6, which is an antiidiotypic single chain antibody mimicking a yeast killer toxin. S. gordonii is a human commensal which we developed as a model system for mucosal delivery of heterologous proteins. The in vivo candidacidal activity of both H6-secreting and H6-surface-displaying streptococcal strains were assayed in a well-established rat model of vaginal candidiasis. At day 21 full clearance of Candida albicans infection was observed in 75% of animals treated with the H6-secreting strain, and in 37.5% of animals treated with the strain expressing H6 on the surface, while all animals treated with the control strain were still infected. The observed candidacidal effect was comparable with that observed with the antimycotic drug fluconazole. These data confirm the potential of H6 as a candidacidal agent and show how promising is the approach of using recombinant bacteria for mucosal delivery of biologically active molecules.     

Phase II clinical trial with Praneem polyherbal tablets for assessment of their efficacy in symptomatic women with abnormal vaginal discharge (an ICMR task force study)

Abnormal vaginal discharge syndrome (AVDS) is a commonly observed gynaecological complaint for which women seek medical attention. The present study was conducted in six Indian Council of Medical Research centres with Praneem polyherbal tablets (PPT), to determine their efficacy in the treatment of symptomatic women with AVDS. Data are given on 141 subjects investigated. In total, 137 women (97%) reported complete (n=62, 44%) and partial (n=75, 53%) relief from symptoms after use of PPT for seven consecutive days. On speculum examination, 71 (74%) women were confirmed to be cured of AVDS. Microbiological tests could only be conducted microscopically for Trichomonas vaginalis, Candida albicans and bacterial vaginosis. It was observed that all women with T. vaginalis had this infection cured by PPT, and the cure rate was 77% for C. albicans and 68% for bacterial vaginosis. Seventy-eight women (55%) reported a transient burning sensation, mostly on the first 2 d of intake of PPT; however, they continued to use the tablets for the prescribed 7 d. This study lays the basis for an extended Phase II/III clinical trial, preferably randomized and comparing a larger number of women to confirm the safety and efficacy of PPT.     

Inhibition of gamma secretase blocks HPV infection

Human papillomaviruses (HPV) are common sexually transmitted pathogens that predispose women to cervical and other anogenital cancers. HPV vaccines can prevent infection by some but not other sexually transmitted HPVs but are too costly for use in much of the world at greatest risk to HPV-associated cancers. Microbicides provide an inexpensive alternative to vaccines. In a high throughput screen, drugs that inhibit the cellular protein complex known as gamma secretase were identified as potential HPV microbicides. gamma Secretase inhibitors (GSIs) inhibited the infectivity of HPV pseudoviruses both in human keratinocytes and in mouse cells, with IC₅₀ values in the picomolar to the nanomolar range. Using a mouse model, we observed that a GSI could inhibit HPV infection to the same degree as its effectiveness in inhibiting gamma secretase activity in vivo. We conclude that gamma secretase activity is required for HPV infection and that GSIs are effective microbicides against anogenital HPVs.     

A Phase I study of the functional performance, safety and acceptability of the BufferGel Duet

BACKGROUND: The purpose of this study was to assess the functional performance of the BufferGel Duet, a buffering microbicide and spermicide gel applied to the cervix and vagina by a novel applicator that also serves as a mechanical barrier. STUDY DESIGN: This was a noncomparative Phase I safety trial in 30 healthy couples, aged 20-50 years, at low risk for sexually transmitted infections, who agreed to use the gel-device combination twice in 1 week and respond to detailed questionnaires about their experience. The female participants were examined with colposcopy before and 6-18 h after using the second device. RESULTS: Based on written instructions alone, 25 women successfully placed and 28 women successfully removed the device. Three women reported feeling the device dislodge around the time of intercourse. The product was equally acceptable to both men and women. Most users concluded that intercourse was the same or better with the device than with no product. About 73% would choose Duet over male condoms, and no one preferred the standard diaphragm. Colposcopic findings were noted in 79% of women with external genital findings (9) or cervicovaginal peeling (18) predominating. Only one finding breached the epithelium. Most product-related adverse events were mild (10/11) and confined to the genitourinary tract. CONCLUSIONS: The successful placements and acceptability suggest that further product development is warranted and could target over-the-counter use. During increased duration of use or more frequent dosing, cervicovaginal monitoring is advised based on the extent of peeling and external colposcopic findings in this short-term study.     

HIV感染者的阴性配偶对杀微生物剂的可接受性研究

目的研究艾滋病病毒（HIV）感染者的阴性配偶,对杀微生物剂的可接受性及相关影响因素。方法采用横断面设计,于2009年5-7月,在云南省德宏州潞西市和盈江县,采用便利抽样选取301名HIV感染者的阴性配偶进行调查。结果共有278名调查对象符合研究标准,47.5%的调查对象表示将来愿意购买并使用杀微生物剂。影响调查对象购买并使用杀微生物剂的因素有：调查对象的阳性配偶近半年是否有外出打工经历,是否参加过HIV相关防治和调查项目,是否愿意使用安全套。具有以下特点的杀微生物剂易被调查对象接受：（1）能安全有效地预防HIV感染;（2）一次使用的价格在5元以下;（3）非处方药;（4）剂型为栓剂。结论调查对象对杀微生物剂的使用态度较积极,但购买需求较低。