A phase I study of a novel potential intravaginal microbicide, PRO 2000, in healthy sexually inactive women

BACKGROUND: Although the male condom provides a reliable means of preventing HIV transmission, a broader choice of methods is required particularly in circumstances where the negotiation of condom use is difficult. Development of new products that may be effective as topical vaginal microbicides is the focus of a great deal of research activity currently. The novel agent PRO 2000, a naphthalene sulphonate derivative with in vitro activity against HIV and other sexually transmissible pathogens, is one such compound. We have studied the local and systemic safety and tolerance of a vaginal gel formulation of this agent at two concentrations (0.5% and 4%) over a 2 week period of daily exposure in two cohorts of healthy sexually abstinent women (one in London, UK, and the other in Antwerp, Belgium). METHODS: This was a randomised, placebo controlled, double blind, three arm clinical trial conducted on two sites. Macroscopic evidence of genital epithelial changes was sought using colposcopy and evidence of microscopic inflammation was acquired using high vaginal biopsy from predetermined sites (UK cohort only). Blood levels of PRO 2000 were measured and laboratory safety tests, including coagulation screens, were performed. The impact on vaginal ecology was also assessed. RESULTS: 73 women were enrolled across both sites (36 UK, 37 Belgium); 24, 24, 25 in the 4%, 0.5%, and placebo groups respectively. Of these, 70 completed 2 weeks' exposure to the study gel. Three (all in the 4% group) withdrew owing to adverse events which were possibly or probably gel related. Cervicovaginal abrasion was seen colposcopically in three subjects after 14 days of gel use (two in the 4% group and one in the placebo group). Genital ulceration was not seen during gel use in any of the subjects who completed the study. Histological evaluation of vaginal biopsy samples (36 women only) showed evidence of increased inflammatory signs in one participant of the 4.0% group. One volunteer in the placebo group had moderate inflammation at screening and at follow up. Severe inflammation was not seen among any of the subjects tested. Plasma levels of PRO 2000 and laboratory safety tests showed no evidence of systemic absorption. No impact was seen on normal vaginal ecology in the UK cohort where samples were taken 12 hours after the last gel application. CONCLUSION: In this phase I study PRO 2000 gel was found to be generally well tolerated with promising local and systemic safety profiles. The 0.5% gel was better tolerated than the 4% gel as fewer genital epithelial adverse events were seen in the former. Phase II studies are about to begin in sexually active women.     

Safety and toxicity of nonoxynol-9 gel as a rectal microbicide

BACKGROUND AND OBJECTIVES: Methods of HIV and STD prevention, which can be controlled by the receptive partner, are a high priority for research and development. Studies on the safety of Nonoxynol-9 (N-9) on the vaginal mucosa have yielded conflicting results. No Phase I study has evaluated the effect of N-9 on the rectal mucosa. GOALS: To assess the safety of 52.5 mg of N-9 in a 1.5-g gel when applied one to four applicators per day to the rectum and penis. STUDY DESIGN: The study included 25 HIV-negative and 10 HIV-positive, monogamous gay male couples in which each partner was exclusively insertive or receptive while using N-9 gel. Each participant served as his own control during placebo gel use compared to during N-9 gel use. Receptive partners underwent anoscopic examination after 1 week of placebo use and after 2, 5, and 6 weeks of N-9 gel use, with rectal biopsies obtained after 1 week of placebo use and after 5 and 6 weeks of N-9 gel use. Insertive partners had safety monitoring after 1 week of placebo use and after 2, 5, and 6 weeks of N-9. RESULTS: No rectal ulcers were detected; superficial rectal erosions were noted in two HIV-negative participants. Abnormal or slightly abnormal histologic abnormalities of rectal biopsies were detected in 31 (89%) receptive participants after N-9 gel use compared to 24 (69%) participants after 1 week of placebo gel use. Meatal ulceration, not caused by herpes simplex virus, was detected in one HIV-negative participant. CONCLUSION: Low-dose N-9 gel was not associated with macroscopic rectal and penile epithelial disruption or inflammation, but histologic abnormalities were commonly observed during N-9 gel as well as during placebo gel use.     

Risk factors for infection with herpes simplex virus type 2: role of smoking,douching, uncircumcised males,and vaginal flora

BACKGROUND: Herpes simplex virus type 2 (HSV-2), the primary cause of genital herpes, is one of the most prevalent sexually transmitted diseases worldwide. Epidemiologic serosurveys suggest that infections occur more frequently in women than in men. GOAL: The goal of the study was to identify unique correlates of HSV-2 infection in women that might contribute to their increased susceptibility of infection or suggest opportunities for decreasing the incidence of disease. STUDY DESIGN: We enrolled 1207 women aged 18 to 30 years from three Pittsburgh health clinics in a cross-sectional study. Each woman provided demographic and behavioral information, vaginal swab specimens for bacterial culture, a vaginal smear for Gram stain diagnosis of bacterial vaginosis, and blood for HSV-1 and HSV-2 serology. RESULTS: Black race, older age, cigarette smoking, douching, a greater number of lifetime sex partners, a history of intercourse with an uncircumcised partner, the presence of vaginal group B Streptococcus, and abnormal vaginal flora were among the independent predictors of HSV-2 infection. CONCLUSION: HSV-2 infection may be occur more often in women who douche, smoke, have sex with uncircumcised partners, or have bacterial vaginosis; these represent alterable risk factors.     

Prevalence of bacterial vaginosis in lesbians and heterosexual women in a community setting

OBJECTIVES: High prevalence of bacterial vaginosis (BV) has been reported in lesbians but most studies were based in sexually transmitted infection clinic settings; therefore, we wished to determine the prevalence and risk factors of BV in lesbians and heterosexual women in a community setting in the UK. METHODS: A cross-sectional study recruiting lesbian women volunteers from community groups, events, clubs and bars. Heterosexual women were recruited from a community family planning clinic. They self-swabbed to create a vaginal smear, which was Gram-stained and categorised as BV, intermediate or normal flora. They completed a questionnaire about age, ethnic group, smoking, genital hygiene practices and sexual history. RESULTS: Of 189 heterosexuals and 171 lesbians recruited, 354 had gradeable flora. BV was identified in 43 (25.7%) lesbians and 27 (14.4%) heterosexuals (adjusted OR 2.45, 95% CI 1.25 to 4.82; p = 0.009). Concordance of vaginal flora within lesbian partnerships was significantly greater than expected (27/31 (87%) couples, kappa = 0.63; p<0.001). Smoking significantly increased the risk of BV regardless of sexuality (adjusted OR 2.65; p = 0.001) and showed substantial concordance in lesbian partnerships but less than for concordance of flora. CONCLUSIONS: Women who identified as lesbians have a 2.5-fold increased likelihood of BV compared with heterosexual women. The prevalence is slightly lower than clinic-based studies and as volunteers were recruited in community settings, this figure may be more representative of lesbians who attend gay venues. Higher concordance of vaginal flora within lesbian partnerships may support the hypothesis of a sexually transmissible factor or reflect common risk factors such as smoking.     

Glycosidase and proteinase activity of anaerobic gram-negative bacteria isolated from women with bacterial vaginosis

BACKGROUND: It is known that glycosidases and proteases are produced by the anaerobic gram-negative bacteria associated with bacterial vaginosis (BV). We hypothesized that these enzymes enzymatically degrade mucins, thereby destroying the mucus gel that otherwise helps protect against sexually transmitted pathogens, including HIV. GOAL: The goal was to determine glycosidase and protease production by vaginal bacteria associated with BV and to compare these with symptoms and signs of abnormal discharge and to test vaginal fluid viscosity. STUDY DESIGN: The anaerobic gram-negative rods recovered from the vaginas of 153 women with normal flora, intermediate flora, or BV were tested for production of sialidase, fucosidase, galactosidase, glucosaminidase, and glycine and arginine aminopeptidases. RESULTS: Women with BV had higher frequencies and concentrations of bacteria producing mucin-degrading enzymes than did women with intermediate and normal flora (P < 0.001). Women with higher concentrations of bacteria producing mucin-degrading enzymes were more likely to have a thin discharge associated with BV (P < 0.001). The viscosity of diluted vaginal fluid samples from women with BV was significantly lower than those from women with normal flora (P = 0.001). CONCLUSION: These data support the hypothesis that BV organisms degrade the protective mucus gel.     

Rectal microbicide acceptability: results of a volume escalation trial

OBJECTIVES: The objectives of this study were to determine what volume of a microbicide placebo gel is acceptable when applied intrarectally before receptive anal intercourse (RAI); and to evaluate responses to properties of the gel, its application, and its use. STUDY DESIGN: HIV-uninfected men who reported unprotected RAI with serodiscordant or unknown-status partners were enrolled in a volume escalation trial. RESULTS: Up to 35 mL of gel with the physical properties of Femglide (transparent and odorless) was acceptable to the majority of participants. Choice of different levels of viscosity may be needed. For some men, volumes judged acceptable when tried without intercourse were not acceptable when used during sex. Overall, participants reported high intentions to use microbicides when available. Condom use was inconsistent despite advice to use condoms. CONCLUSIONS: Microbicides that would require up to 35 mL of volume to be effective would be acceptable to men who engage in high-risk RAI.     

Douching and endometritis: results from the PID evaluation and clinical health (PEACH) study

BACKGROUND: Douching has been related to risk of pelvic inflammatory disease (PID). GOAL: To examine the association between douching and PID in a large, multicenter, clinical trial of PID after adjustment for race/ethnicity. STUDY DESIGN: Interviews were conducted with 654 women who had signs and symptoms of PID. Vaginal Gram stains and upper genital tract pathology/cultures were obtained from all the women. Women with evidence of plasma cell endometritis and/or gonococcal or chlamydial upper genital tract infections were compared with women who had neither endometritis nor upper genital tract infection. RESULTS: Women with endometritis or upper genital tract infection were more likely to have douched more than once a month or within 6 days of enrollment than women who never douched. These associations remained after adjustment for confounding factors, after analysis of black women only; and among women with normal or intermediate vaginal flora but not bacterial vaginosis. CONCLUSION: Among a predominantly black group of women with clinical PID, frequent and recent douching was associated with endometritis and upper genital tract infection.     

Treatment of male partners and recurrence of bacterial vaginosis: a randomised trial.

OBJECTIVE: To test the efficacy of treatment with clindamycin of a partner on the recurrence rate of bacterial vaginosis in women within 3 months from diagnosis. SUBJECTS: Eligible for the study were sexually active women with one current sexual partner, who were aged 18-45 years, with a clinical diagnosis of bacterial vaginosis and whose partner agreed to be treated. METHODS: A double blind, randomised, controlled trial was conducted comparing the effect of treating the partner with either clindamycin capsules or placebo on the reduction of the recurrence rate of bacterial vaginosis. Women were treated with clindamycin 2% vaginal cream, administered intravaginally once daily at bedtime for 7 consecutive days. The partners were randomly allocated to clindamycin hydrochloride capsules, 150 g by mouth four times daily for 7 consecutive days, or a placebo. A total of 139 couples were randomised--69 were treated with clindamycin vaginal cream group and 70 with placebo. One, 4, and 12 weeks after the end of treatment the patients and their partners were examined; vaginal discharges were examined to check for clue cells, vaginal pH was determined, and a KOH test carried out. RESULTS: Overall, 131 women out of the 139 who entered the study were cured (94.2%, lower 95% confidence interval 79.8, based on Poisson's approximation). There was no difference in the cure rate among women whose partner received clindamycin or placebo (chi(2) p = not significant). A total of 55 couples (26 in the clindamycin and 29 in the placebo group) withdrew from the study during the follow up period. Of the 69 women whose partner received clindamycin, 22 (31.9%) reported "recurrence" or persistence. The corresponding number was 21 (30%) of the 70 women whose partner received placebo (chi(2) p = not significant). Of the 84 couples in which the woman was cured by the first week's visit and who completed the study; there were five recurrences (11.6%) among the 43 women whose partner received clindamycin and nine (22.0%) of the 41 whose partner received placebo (chi(2) p = not significant). CONCLUSION: This study indicates that vaginal clindamycin is effective and safe in the treatment of bacterial vaginosis, but it does not support the suggestion that male treatment markedly reduces the short term recurrence rate.     

深圳市已婚育龄夫妇性生活现状调查

目的：了解深圳市已婚育龄夫妇性生活状况及影响性功能的生活、职业、环境因素。方法：利用深圳市人口和计划生育局的育龄夫妇信息系统,使用随机抽样法,抽取已婚育龄夫妇424对为研究对象,培训社区调查员后对研究对象进行入户调查,采用Epidata 3．0软件建立数据库并录入问卷,使用SPSS13．0对数据进行统计分析。结果：1）被调查的已婚育龄夫妇中夫妻双方至少一方存在性生活问题的有149对,占总体的41．6％;而至少存在一个性生活问题的女性有136人（36．1％）,高于男性的72人（19．4％）;2）女性（8．3％）比男性（2．4％）更容易出现性交痛（P〈0．05）。在性高潮障碍方面,女性（11．3％）比男性（5．8％）也更不容易达到性高潮（P〈0．05）;3）被调查的影响夫妻双方性生活因素中,年龄是最主要的因素,随着年龄增大,性生活更容易出现问题,夫妻双方的教育程度越高,性生活满意度越高,而家庭收入对性生活影响不显著;4）当性生活遇到问题时,极少数女性（3．1％）和男性（4．0％）会寻求医疗帮助和心理帮助。结论：已婚育龄夫妇性生活状况较差,约有41．6％夫妻至少一方出现了性生活问题,女性比男性更容易出现性生活问题;年龄和教育程度是影响性生活的重要因素,家庭收入则对性生活影响较小。     

A randomized six-day safety study of an antiretroviral microbicide candidate UC781, a non-nucleoside reverse transcriptase inhibitor

GOAL: This study evaluated the effect of a single dose and 5 additional consecutive daily doses of UC781 gel at concentrations of 0.1%, 0.25%, 1.0%, and 0% on urogenital irritation. STUDY DESIGN: Forty-eight healthy sexually abstinent women were randomly assigned to 1 of 4 groups. METHODS: Urogenital irritation was assessed by pelvic examination, colposcopy, and reports of genital symptoms at baseline and after 1 and 6 doses. Vaginal health was assessed by wet mount and systemic safety by laboratory evaluation after 1 and 6 doses, and UC781 levels were assessed at baseline and after 6 doses. RESULTS: Some evidence of urogenital irritation was common in all treatment groups and was most often transient and mild. Colposcopic findings were infrequent in the placebo group (8%) and more common in the 3 treatment groups (24%-42%). Edema, which may indicate underlying inflammation, was observed in the vaginal fornix of 2 women exposed to UC781. There was no apparent increase in vaginal infection or clinically significant changes in laboratory values. Two of 12 participants randomized to 1% UC781 gel had detectable plasma levels that were less than the lower level of quantification. CONCLUSIONS: UC781 was well tolerated in this initial dose ranging safety study when used once daily for 6 days in sexually abstinent women. Five safety/pharmacokinetic studies of UC781 are currently underway in women and men, all utilizing UC781 concentrations less than 1%, with twice-daily dosing in some studies, and all involving careful monitoring of exposed epithelium.     

Safety trial of the vaginal microbicide cellulose sulfate gel in HIV-positive men

OBJECTIVE: Cellulose sulfate (CS) is a promising vaginal microbicide. Because men will be exposed to the microbicide when engaging in vaginal intercourse, safety and acceptability need to be assessed in men. DESIGN: This randomized double-blind phase I study assessed the safety and acceptability of seven consecutive daily doses of CS versus KY Jelly in 36 HIV-positive men. RESULTS: No new or worsening of existing genital findings were observed during the follow-up examination. Mild genital symptoms were reported in 42% of CS users (itching, burning, tingling, testicular pain, dysuria, and warm or cold feeling) and 8% of KY Jelly users. CONCLUSION: CS gel applied to the penis was well tolerated in this HIV-positive male population. The itching and burning symptoms were not severe and can be explained by the preservative benzyl alcohol present in the CS gel.     

A prospective study of risk factors for bacterial vaginosis in HIV-1-seronegative African women

BACKGROUND: Bacterial vaginosis (BV) is common and has been associated with increased HIV-1 susceptibility. The objective of this study was to identify risk factors for BV in African women at high risk for acquiring HIV-1. METHODS: We conducted a prospective study among 151 HIV-1-seronegative Kenyan female sex workers. Nonpregnant women were eligible if they did not have symptoms of abnormal vaginal itching or discharge at the time of enrollment. At monthly follow-up, a vaginal examination and laboratory testing for genital tract infections were performed. Multivariate Andersen-Gill proportional hazards analysis was used to identify correlates of BV. RESULTS: Participants completed a median of 378 (interquartile range 350-412) days of follow-up. Compared with women reporting no vaginal washing, those who reported vaginal washing 1 to 14 [adjusted hazard ratio (aHR) 1.29, 95% confidence interval (CI) 0.88-1.89], 15 to 28 (aHR 1.60, 95% CI 0.98-2.61), and >28 times/wk (aHR 2.39, 95% CI 1.35-4.23) were at increased risk of BV. Higher BV incidence was also associated with the use of cloth for intravaginal cleansing (aHR 1.48, 95% CI 1.06-2.08) and with recent unprotected intercourse (aHR 1.75, 95% CI 1.47-2.08). Women using depot medroxyprogesterone acetate contraception were at lower risk for BV (aHR 0.59, 95% CI 0.48-0.73). CONCLUSIONS: Vaginal washing and unprotected intercourse were associated with increased risk of BV. These findings could help to inform the development of novel vaginal health approaches for HIV-1 risk reduction in women.     

The Bali STD/AIDS study: association between vaginal hygiene practices and STDs among sex workers

OBJECTIVES: To assess the association between genital cleansing practices and the prevalence of sexually transmitted diseases and of sexual health knowledge among female sex workers in Bali, Indonesia. METHODS: Low priced commercial sex workers (CSWs) participated in the Bali STD/AIDS Study, a 3 year educational project evaluating the effect of education on the subsequent use of condoms and the prevalence of STDs and AIDS. Structured interviews, genital evaluation, laboratory evaluation for STDs, and treatment were performed. Vaginal cleansing characteristics including frequency, type, and reasons for use, were evaluated. Associations between these characteristics and the presence of bacterial and viral genital infections were assessed. RESULTS: Of 625 female sex workers evaluated between May and July 1998, 99.1% used substances, such as soap and toothpaste, to clean the vagina at least daily, with 69.3% performing this after each intercourse. The women using such cleansers after each client did not differ from those using them once or less daily in education, AIDS and condom use knowledge, time working as a CSW, or number of clients in the previous day. However, they were younger than those using vaginal cleansers daily or less, and reported lower condom usage in the past week. Several genital symptoms, such as discoloured discharge and odour, were reported less by women with the highest frequency of vaginal cleanser use. Prevalence of genital infections in this population of women was substantial, with bacterial infections more prevalent than viral infections. Infections were not associated with the type of cleanser used, using a genital cleanser on the day of examination, or using a cleanser after each client versus daily or less, except for candida colonisation, which was more prevalent in women cleansing after each client (OR=1.87, 95% CI 1.21, 2.90). However, symptomatic candida vulvovaginitis (positive culture plus presence of symptoms) was not associated with the prevalence of genital cleansing. Women using genital cleansing in part for "infection avoidance" (39.7%) were more likely to have heard of STDs and AIDS, but were less knowledgeable about these infections, compared with women not citing this reason for genital cleansing. CONCLUSION: Commercial sex workers in low priced brothels in Bali have a high rate of genital infections, with lower rates of viral compared with bacterial infections. Genital cleansers, on a daily or after each intercourse schedule, are used routinely. Although genital cleansing after each intercourse was associated with fewer genital symptoms, the prevalence of STDs did not differ significantly based on this frequency, and the women's knowledge of STDs and AIDS was less than that of women cleansing less often. The effect of genital cleansing in general on STD and AIDS prevalence could not be assessed in this population owing to the lack of a non-cleansing cohort. Further study to elucidate the effect of vaginal cleansing practices on STD prevalence and resistance is needed.     

Acceptability of a bioadhesive nonoxynol-9 gel delivered by an applicator as a rectal microbicide

BACKGROUND AND OBJECTIVES: Potential rectal microbicides, as an adjunct to condoms for HIV/STD prevention, have not been studied previously. GOAL OF THIS STUDY: Advantage 24 (1.5 ml of a bioadhesive gel containing 52.5 mg nonoxynol-9 administered by single-use applicator)-under investigation as a vaginal microbicide-was evaluated for acceptability among male couples. STUDY DESIGN: Twenty-five HIV-negative and 10 HIV-positive male couples participated in a frequency use escalation trial. Diaries and self-administered questionnaires assessed product use, acceptability, sexual behavior, and gastrointestinal and urologic side effects. RESULTS: Excluding participants who felt no need for an HIV prevention method, 58% said they would use Advantage 24 if approved for rectal use; 69% of receptive users reported rectal fullness and related side effects after insertion of the gel, and 68% reported applicator-related discomfort; 59% of insertive participants found the gel too sticky. CONCLUSIONS: Acceptability remains inconclusive and warrants further study of redesigned applicators and ways to minimize rectal side effects.     

Preliminary safety and acceptability of a carrageenan gel for possible use as a vaginal microbicide

OBJECTIVE: We sought to determine the safety and acceptability of vaginal gel formulation PC-503 among low risk, abstinent women. The active ingredient was 2% pharmaceutical grade lambda carrageenan, a sulphated polymer that is generally recognised as safe by the US Food and Drug Administration. METHODS: 35 women in five sites applied 5 ml of the PC-503 gel vaginally once a day for 7 days while abstaining from sexual intercourse. Visual vaginal examinations were performed on days 1, 4, and 8. STI testing and vaginal pool Gram stain preparations were done on days 1 and 8. Participants were asked about product acceptability. RESULTS: 34 of the 35 women enrolled completed 7 days' use. Following product use, five reported mild symptoms including "bladder fullness," "genital warmth," or discomfort, and lower abdominal pain, and one had moderate pale yellow cervical discharge. Using the Nugent criteria, three women had bacterial vaginosis (BV) before and after use; three had BV before but not after, and two had BV after but not before. Most of the women found PC-503 to be pleasant or neutral in feel and smell and considered extra lubrication to be an advantage; however, one third found it to be messy. CONCLUSIONS: Vaginal use of PC-503 gel did not cause significant adverse effects in a small number of low risk, sexually abstinent women. Further testing in larger numbers of sexually active women is planned. A smaller volume of gel may be more acceptable to some women.     

Asymptomatic non-ulcerative genital tract infections in a rural Ugandan population

OBJECTIVE: To document the prevalence of asymptomatic non-ulcerative genital tract infections (GTI) in a rural African cohort. METHODS: The study population consisted of all adults aged 15-59 residing in 56 rural communities of Rakai District, southwest Uganda, enrolled in the Rakai STD Control for AIDS Prevention Study. Participants were interviewed about the occurrence of vaginal or urethral discharge and frequent or painful urination in the previous 6 months. Respondents were asked to provide blood and a first catch urine sample. Serum was tested for HIV-1. Urine was tested with ligase chain reaction (LCR) for N gonorrhoeae and C trachomatis. Women provided two self administered vaginal swabs; one for T vaginalis culture and the other for a Gram stained slide for bacterial vaginosis (BV) diagnosis. RESULTS: A total of 12,827 men and women were enrolled. Among 5140 men providing specimens, 0.9% had gonorrhoea and 2.1% had chlamydia. Among 6356 women, 1.5% had gonorrhoea, 2.4% had chlamydia, 23.8% were infected with trichomonas and 50.9% had BV.53% of men and 66% of women with gonorrhoea did not report genital discharge or dysuria at anytime within the previous 6 months. 92% of men and 76% of women with chlamydia and over 80% of women with trichomonas or BV were asymptomatic. The sensitivities of dysuria or urethral discharge for detection of infection with either gonorrhoea or chlamydia among men were only 21.4% and 9.8% respectively; similarly, among women the sensitivity of dysuria was 21.0% while that of vaginal discharge was 11.6%. For trichomonas or BV the sensitivity of dysuria was 11.7% and that of vaginal discharge was 10.5%. CONCLUSION: The prevalence of non-ulcerative GTIs is very high in this rural African population and the majority are asymptomatic. Reliance on reported symptoms alone would have missed 80% of men and 72% of women with either gonorrhoea or chlamydia, and over 80% of women with trichomonas or BV. To achieve STD control in this and similar populations public health programmes must target asymptomatic infections.     

Vaginal and rectal topical microbicide development: safety and efficacy of 1.0% Savvy (C31G) in the pigtailed macaque

BACKGROUND: A 1.0% gel formulation of C31G, a surfactant, has been shown to have in vitro antiviral and antibacterial activity. GOAL: The goal of this study was to evaluate the safety and efficacy of vaginal and rectal applications of 1.0% Savvy (C31G) in the nonhuman primate model. STUDY DESIGN: The safety of repeated 1.0% C31G application was evaluated by microflora, pH, vaginal biopsy, colposcopy, and rectal lavage. Efficacy in preventing chlamydial infection was documented by culture, nucleic acid amplification tests, and serology. RESULTS: Repeated applications of Savvy (1.0% C31G) were not associated with significant changes in pH, microflora, or inflammatory infiltrates on tissues. No significant differences in epithelial desquamation were noted after rectal product use compared with placebo. Four of 6 animals were protected from chlamydial infection after pretreatment with Savvy. C31G was shown to be safe to both vaginal and rectal mucosal tissues and to the microflora with repeated daily use. CONCLUSION: Savvy has an acceptable safety profile after repeated vaginal and rectal use. A single intravaginal application of 1.0% C31G provided partial protection from acquiring cervical chlamydial infection.     

A randomized, double-blind clinical trial of vaginal acidification versus placebo for the treatment of symptomatic bacterial vaginosis

BACKGROUND AND OBJECTIVES: Vaginal acidification has been suggested as a means of normalizing the vaginal flora. GOAL: The purpose of this study was to determine the effectiveness of an acetic acid-based vaginal gel in the treatment of bacterial vaginosis (BV). STUDY DESIGN: Forty-four patients with BV were enrolled in a randomized, double-blind clinic trial. Of these, 29 were evaluable. Patients were randomized to receive either 5 mL acetic acid gel (n = 14) or placebo gel (n = 15) intravaginally twice daily for 7 days. Clinical criteria and vaginal Gram stain scores were compared between the initial visit and at 2 weeks after initiating therapy. RESULTS: No significant differences were noted when comparing drug and placebo in terms of subjective or clinical improvement or improvement in Gram stain smears for bacterial vaginosis. CONCLUSION: Vaginal acidification with an acetic acid gel formulated to pH 3.9 to 4.1 was ineffective therapy for bacterial vaginosis.     

What is normal vaginal flora?

OBJECTIVE: To observe the composition of the vaginal flora of healthy women over time, and in relation to hormonal changes, sexual activity, and hygiene habits. DESIGN: A longitudinal surveillance of the vaginal flora over an eight week period. SUBJECTS: 26 female health care workers in local genitourinary medicine clinics. METHODS: The participants were anonymised. They filled in diary cards daily. Blind vaginal swabs were self-taken two-seven times weekly. A smear was air-dried for later Gram staining. The swabs were also cultured for Candida spp, Gardnerella vaginalis, anaerobes, Mycoplasma hominis and Ureaplasma urealyticum. RESULTS: Of 26 subjects, only four had normal vaginal microbiology throughout. One woman, who was not sexually active, had bacterial vaginosis (BV) throughout and nine (35%) had intermittent BV. Candidiasis was found intermittently in eight women (31%), and eight had normal microscopy. U urealyticum was isolated intermittently in 40% of women with BV, 25% with candida, and 50% with normal microscopy. Many women were symptomatic, but symptoms correlated poorly with microbiological findings. All but two women were sexually active; however, more women with BV were exposed to semen. BV seemed to be related to frequent use of scented soap, and there appeared to be an additive effect of clothing and hygiene factors. CONCLUSIONS: Our study raises doubts about what should be regarded as normal vaginal flora. It calls into question the significance of finding BV or U urealyticum on a single occasion in asymptomatic women, or of finding normal flora in symptomatic women. The effect of external factors on the vaginal flora deserve further study.     

Consistency of self-reported sexual behavior and condom use among current sex partners

OBJECTIVE: The objective of this study was to determine concordance in sex partner reports of frequency of vaginal and oral intercourse and condom use. STUDY DESIGN: Self-reported behaviors among 112 women treated for urinary tract infection (UTI), sore throats, or receiving birth control at a student health service were compared with that of their current sex partner. RESULTS: Correlation was excellent for frequencies of vaginal intercourse (r = 0.88), cunnilingus (r = 0.72), fellatio (r = 0.76), and condom use (r = 0.86), but women with UTI compared with women without UTI reported greater frequency of sexual activity than their sex partner. This effect overwhelmed the modest increases in correlation associated with duration of relationship and marital status. CONCLUSIONS: Women with genitourinary symptoms may over-recall frequency of sexual behavior compared to women without these symptoms. Knowing the extent of this recall bias will assist in the interpretation of data and appropriate correction of parameters when included in prediction models.