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Interleukins (IL)-8, IL-1α, IL-1β, and IL-1 receptor antagonist (IL-1RA) have emerged as indicators of vaginal inflammation and HIV-1 transmission risk. We provide values and factors of normal variation of these immune mediators in premenopausal women to allow their wider clinical application as biomarkers of vaginal health. Cross-sectional analyzes (Kruskal-Wallis and Wilcoxon exact tests) of cytokine concentrations in relation to sociodemographic variables and Nugent score were performed on baseline (prior to product) cervicovaginal lavage from two Phase I randomized microbicide trials. All women in the analysis had regular menstrual cycles, 72 h abstinence, normal blood and Pap tests, and absence of genitourinary infections, study-relevant allergies, antibiotics use and history of substance abuse. Cytokine norms were defined as the values among those with Nugent score <4. Among women with normal Nugent score (n=92), IL-8 and IL-1β were lowest in those using abstinence as compared to hormonal contraceptives or male/female sterilization as their primary method for birth control. No difference was found by age, prior pregnancy, or education, and also by race after controlling for contraceptive method. Women with abnormal (>7) and borderline (4-6) Nugent scores had elevated IL-1α and/or IL-1β although their IL-1RA-to-IL(α+β) ratio remained within the normal range due to higher IL-1RA. Women with borderline Nugent scores had IL-8 levels above the normal range. IL-8 and the IL-1RA-to-IL-1 ratio can be used as independent biomarkers of vaginal immune balance. More studies must determine the role of sexual activity, contraceptive method, and borderline Nugent scores, which normally are not exclusion criteria for enrollment in microbicide trials but may affect product tolerability and HIV-1 risk due to the aberrant cytokine levels., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Objectives: Nigerian women reportedly apply lime juice intravaginally to protect themselves against HIV. In vitro data suggest that lime juice is virucidal, but only at cytotoxic concentrations. This is the first controlled, randomized safety trial of lime juice applied to the human vagina., Methods: Forty-seven women were randomized to apply water or lime juice (25%, 50%, or undiluted) intravaginally twice daily for two 6-day intervals, separated by a 3-week washout period. Product application also was randomized: during 1 interval, product was applied using a saturated tampon and in the other by douche. Vaginal pH, symptoms, signs of irritation observed via naked eye examination and colposcopy, microflora, and markers of inflammation in cervicovaginal lavages were evaluated after 1 hour and on days 3 and 7., Results: The largest reduction in pH was about one-half a pH unit, seen 1 hour after douching with 100% lime juice. We observed a dose-dependent pattern of symptoms and clinical and laboratory findings that were consistent with a compromised vaginal barrier function., Conclusions: The brief reduction in pH after vaginal lime juice application is unlikely to be virucidal in the presence of semen. Lime juice is unlikely to protect against HIV and may actually be harmful.

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.

Background: C31G is a broad-spectrum antibacterial agent that shows contraceptive properties in vitro. This postcoital testing study evaluated the ability of three C31G concentrations, 0.5%, 1.0% and 1.7%, administered as a 3.5-mL dose of a vaginal gel to prevent sperm from entering mid-cycle cervical mucus. Irritation of the genitalia and acceptability were also assessed., Method: At baseline, a mid-cycle cervical mucus test and a postcoital test were performed within 24 h of each other without use of any study products to establish normal mid-cycle cervical mucus and sperm penetration. Subjects then completed up to three test cycles using one of the three concentrations of study product during intercourse., Results: Twenty-two of the 61 women enrolled completed a baseline cycle and at least one test cycle. An average of 14.6 progressively motile sperm per high power field was seen at baseline. This was reduced to 0.3 after use of 0.5% C31G, 0.5 after use of 1.0% C31G, and 0.4 after use of 1.7% C31G. There was no significant difference between test products (p >/= 1.000) but each test product was significantly different from baseline (p < 0.002). Very little genital irritation was observed. There were more reports of leakage and messiness with increasing C31G concentration., Conclusion: This study suggests that all three concentrations of C31G are likely to give reasonable results in a contraceptive effectiveness trial. Based on the results of this and other trials, the 1.0% concentration has been selected for further development, including Phase III trials of contraceptive effectiveness.

Background: C31G is an antimicrobial and spermicidal agent that contains two surface-active compounds, cetyl betaine and myristamine oxide. It is being developed as a vaginal microbicide and contraceptive., Method: Three C31G concentrations (0.5%, 1.0% and 1.7%) were tested and compared with Extra Strength Gynol II(R), a marketed spermicide containing 3% nonoxynol-9 (N-9), in a randomized, double-blinded, Phase I, dose-escalation study to assess genital irritation (by subject report, visual examination at pelvic examination and colposcopy), plasma and vaginal lavage levels of C31G, product leakage, systemic safety and acceptability. Women were randomized to use 3.5 mL of one of the three C31G products or the N-9 gel at night for 7 days then twice daily for another 7 days. Pelvic and colposcopic evaluations were performed after 7 and 14 days of product use., Results: The percent of women experiencing irritation in the 0.5% and 1.0% C31G groups in the study were similar to each other and were lower than the percent experiencing irritation in the 1.7% and N-9 groups, which were also similar to each other. Differences were statistically significant between 1.0% C31G vs. N-9 at 7 days and between 0.5% C31G and 1.0% C31G vs. N-9 at 14 days. There was no significant difference between groups in leakage or acceptability. No C31G was detected in the plasma of any volunteer., Conclusions: These results suggest that 0.5% and 1.0% C31G are less irritating to the female genital tract than 1.7% C31G or Extra Strength Gynol II.

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.

Objectives: FemCap is a silicone-rubber barrier contraceptive approved for marketing in the United States. To address reported problems with removal and dislodgment, the device's developer added a strap to the device and increased the height of the brim. This trial assessed whether the new design reduced removal difficulties and had any effects on dislodgment, genital pain/discomfort, safety, and acceptability.Methods: Women used the strapped device for 8 weeks with follow-up visits at 2 and 8 weeks. Outcome measures were obtained through diary cards, questionnaires, and naked eye examination. Data from these 120 women were compared with data from 419 women who used the unstrapped FemCap in a previous contraceptive effectiveness study.Results: The strapped device was not significantly easier for users to remove than the unstrapped device. Similar odds of dislodgment and cervical/vaginal irritation were seen with the two devices. Both female and male participants were significantly more likely to report pain/discomfort with use of the strapped device. Female users of the strapped device were significantly more likely to say they disliked their device. In six weeks, two pregnancies were observed, but pregnancy was not an endpoint in the study and no conclusions should be drawn regarding pregnancy rates.Conclusions: The modifications to the FemCap did not significantly improve the ease of device removal and appears to have resulted in significantly more female and male partner pain/discomfort and decreased acceptability, compared with the unstrapped device. [ABSTRACT FROM AUTHOR]

Abstract: Objectives: The aims of this study were to assess the effects of Lea''s Shield® plus nonoxynol-9 spermicide on signs and symptoms of female genital irritation and cervical and vaginal microflora during 8 weeks of use with intercourse and to analyze problems associated with the use of the device. Methods: In this open-label, single-arm study, participants were evaluated by pelvic examination, colposcopy and vaginal and cervical cultures. Results: About 13% of women (4/30) reported symptoms of irritation, and minor product-related colposcopic findings were seen in about one third (11/30). Although average colony counts for enterococcus, Escherichia coli and anaerobic gram-negative rods increased during product use, no clinical diagnoses of infection were made. Most users reported at least one problem using Lea''s Shield. Conclusion: Lea''s Shield, when used for 8 weeks during intercourse, is associated with evidence of genital irritation in a minority of users and with changes in vaginal microflora that do not appear to correlate with clinical infections. [Copyright &y& Elsevier]