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An objective and accurate method that measures adherence to vaginal microbicide gel regimens during clinical trials could provide more accurate estimates of microbicide efficacy, aid in targeting adherence promotion resources, and enable objective assessment of adherence promotion strategies.We evaluated 4 methods to assess whether or not gel applicators had been vaginally inserted. At the study site, 50 women inserted hydroxyethylcellulose universal placebo gel through a polypropylene vaginal applicator and handled, but did not insert a second "sham-inserted" applicator. Applicators were discarded into a container capped with a medical event monitor system (MEMS) that recorded the time and date of opening. Fifteen additional participants did likewise at 2 study site visits, and administered gel on 6 intervening days at home. Applicators were scored as inserted, or not, by direct inspection under ambient light, ultraviolet (UV) light, staining with Alcian blue, and microscopic detection of vaginal cells stained with iodine.Mean sensitivity/specificity of 2 readings each by 3 test readers for UV, Alcian blue, ambient light, and iodine methods were 84/83, 79/83, 76/63, and 65/80%, respectively. Sensitivity of all methods was significantly higher in applicators inserted after one or more prior insertions of gel, with the highest sensitivity (95%) obtained with UV. MEMS caps accurately recorded applicator disposal time.The modest accuracy of all 4 methods for applicator insertions without prior gel applications may limit their accuracy in monitoring coital regimens. However, for daily dosing regimens, MEMS monitoring and UV inspection should provide a rapid, reliable, and quantitative assessment of adherence.

Background: Developing effective and safe microbicides requires study procedures (e.g., technology used, abstinence requirements, and product use) that are acceptable to participants. Methods: Thirty women completed 4 study visits including pelvic examination, colposcopy, optical coherence tomography (OCT), and semistructured, qualitative interviews. Additional requirements included abstinence (for approximately 16 days) and twice daily vaginal product use (for 5.5 days). Interviews were audio-recorded, transcribed, and analyzed using framework analysis. Themes addressing OCT experiences, acceptability of abstinence, and vaginal product use were examined. Results: OCT was viewed favorably as an imaging technology. Some women reported feeling the fiber-optic probe “poking” them and more than one-third spontaneously reported feeling pressure or pinching upon rotation of the speculum in connection with the OCT evaluation. Compliance with vaginal gel use was high, but for many women assigned to use a product containing nonoxynol-9 (vs. placebo), the postproduct use examination was more uncomfortable, relative to the initial examination or 1 week following product discontinuation. Nearly all women experienced product leakage; acceptability of leakage varied. Two women were not abstinent and several more found abstinence challenging. Some women involved their partner in decision making regarding trial enrollment. Strategies to remain abstinent included participating when the partner was away, avoiding early intimacy, and engaging in alternative sexual activities. Conclusions: Qualitative interviews in early-phase studies provide insights and capture information that would be missed by behavioral inference alone. Understanding participant's experiences is important in order to provide anticipatory guidance and plan future microbicide studies that facilitate adherence with trial requirements.

The rate of HIV transmission is increasing more in women than in any other group. There is an urgent need for the development of microbicides with activity against this virus that women can use during intercourse. These products must be convenient effective and safe and ideally they will cause minimal disruption in the normal vaginal ecosystem. The objective of this study was to evaluate changes in vaginal microflora specifically Lactobacillus species with the use of BufferGel. A prospective cohort study was performed to evaluate the change in vaginal flora before and after BufferGel use. BufferGel was applied vaginally once or twice daily for 14 days by low-risk abstinent and monogamous women. There was no change in frequency of Lactobacillus species after BufferGel use. However there was a decrease in H/2O/2-producing lactobacilli (from 4.9 x 10/7 to 1.1 x 10/7 cfu; P = 0.001). The proportion of facultative gram-negative rods present increased from 27% to 65% after BufferGel use whereas obligately anaerobic microbes decreased from 62% to 38%. Use of BufferGel once or twice daily for 14 days resulted in no clinically significant change in Lactobacillus colonization. (authors)

Background Studies of vaginal physiology and pathophysiology sometime require larger volumes of undiluted cervicovaginal secretions than can be obtained by current methods. A convenient method for self-sampling these secretions outside a clinical setting can facilitate such studies of reproductive health. Goal The goal was to develop a vaginal self-sampling method for collecting large volumes of undiluted cervicovaginal secretions. Study design A menstrual collection device (the Instead cup) was inserted briefly into the vagina to collect secretions that were then retrieved from the cup by centrifugation in a 50-ml conical tube. Results All 16 women asked to perform this procedure found it feasible and acceptable. Among 27 samples, an average of 0.5 g of secretions (range, 0.1-1.5 g) was collected. Conclusions This is a rapid and convenient self-sampling method for obtaining relatively large volumes of undiluted cervicovaginal secretions. It should prove suitable for a wide range of assays, including those involving sexually transmitted diseases, microbicides, vaginal physiology, immunology, and pathophysiology.

Background: Microbicides are being developed for woman-controlled protection against sexually transmitted diseases (STDs). Goal: The goal of the study was to test candidate microbicides in a mouse model for preventing vaginal transmission of Chlamydia trachomatis and for acute toxicity to columnar epithelium. Study Design: Progestin-sensitized CF-1 mice were treated vaginally with 50 μl of microbicide, followed either by vaginal inoculation with 10 ID 50 of C trachomatis serovar D or by examination of the epithelial surface for acute toxicity with a viability stain (ethidium homodimer-1). Results: Nonoxynol-9 (N9), sodium dodecyl sulfate (SDS), chlorhexidine digluconate, and BufferGel all provided significant though incomplete protection against vaginal transmission. Other candidates, all of which were effective in vitro, provided no vaginal protection: κ-darrageenan, dextran sulfate, polystyrene sulfonate, Concanavalin A, wheat germ agglutinin, and Phaseolus vulgaris agglutinin. The surface-active agents (N9, SDS, and chlorhexidine) caused significant acute epithelial toxicity: 3 days after chlorhexidine exposure, mice also had vaginal friability and markedly increased susceptibility to Chlamydia. BufferGel was the only candidate tested that was both protective and relatively nontoxic. Conclusion: Microbicides can provide vaginal protection against Chlamydia in highly susceptible progestin-sensitized mice. Since N9 does not inactivate Chlamydia, it likely protects by killing target cells in the vagina. Despite the ability to both potently inactivate Chlamydia and kill target cells, two surface-active agents, SDS and chlorhexidine, failed to provide complete protection, a circumstance which emphasizes the importance of distributing microbicides to all susceptible surfaces.

BufferGel is a novel spermicidal and microbicidal gel formulated to maintain the natural protective acidity of the vagina by acidifying semen, which otherwise alkalinizes the vagina.To test the efficacy of BufferGel for preventing sexually transmitted infections and pregnancy in animal models.Animals were challenged with pathogens or sperm after pretreatment with both test and control agents, or after no pretreatment, then evaluated for infection or pregnancy using standard methods.BufferGel provided significant contraceptive efficacy in the rabbit, and significant protection against vaginal and rectal transmission of herpes simplex virus type 2 (HSV-2) in the mouse, vaginal transmission of Chlamydia trachomatis in the mouse, and skin transmission of cottontail rabbit papillomavirus in the rabbit. It did not protect against vaginal transmission of Neisseria gonorrhoeae in the mouse.The protective efficacy of BufferGel in five of the six animal models suggests that this microbicide warrants clinical evaluation for both contraception and disease prevention.