Effect of treatment assignment on intravaginal cleansing in a randomized study of the diaphragm with candidate microbicide.

BACKGROUND: Intravaginal cleansing may predispose women to adverse health outcomes and may interfere with the effectiveness and safety of female-initiated methods for preventing sexually transmitted infections (STIs). In a 4-week randomized study of 192 Malagasy sex workers, we evaluated associations between self-reported intravaginal cleansing and randomization assignment: diaphragm with viscous candidate microbicide gel (Acidform™, TOPCAD, Chicago, IL, licensed to Instead, Coppell, TX), diaphragm with placebo hydroxyethylcellulose gel (HEC, ReProtect LLC, Baltimore, MD), Acidform alone, or HEC alone. METHODS: Women were counseled to avoid intravaginal cleansing and were blinded to gel assignment. We evaluated changes in self-reported intravaginal cleansing across the study and assessed the effects of treatment assignment and covariates on frequent (more than once daily) intravaginal cleansing. Significant predictors in domain-specific models were evaluated in an all-domain multiple regression model. RESULTS: The proportion of women reporting intravaginal cleansing decreased from baseline (97%) to week 1 (82%) (p < 0.001). Self-reported frequent intravaginal cleansing decreased from baseline (87% to 56%) during the same time period (p < 0.001). In adjusted analyses, the Acidform-diaphragm group had 60% lower odds of frequent intravaginal cleansing during the study (odds ratio [OR] 0.4, 95% confidence interval [CI] 0.2-0.8) compared to the control group (HEC only). HEC-diaphragm and Acidform only users did not differ from controls. Living on the coast of Madagascar, not cohabiting, frequent intravaginal cleansing at enrollment, and high coital frequency predicted frequent intravaginal cleansing during follow-up. CONCLUSIONS: Gel characteristics and the diaphragm's presence likely influenced women's cleansing. Viscous gel delivered by a cervical barrier (such as a diaphragm) may minimize the likelihood of frequent intravaginal cleansing.

Diaphragm for STI and HIV prevention: is it a safe method for women at high risk?

Female sex workers (n = 140) were enrolled in a 6-month acceptability trial of the diaphragm. We randomized a subset (n = 40) to receive colposcopies after 1 month of diaphragm use or after 1 month of observation before commencing diaphragm use. Adverse events were mild in nature. Frequency of colposcopic findings did not differ between women randomized to immediate versus delayed diaphragm use (P = 0.25).

Unmet need for contraception among sex workers in Madagascar.

BACKGROUND: The study was conducted to investigate past and future pregnancy preferences and contraceptive need among Malagasy sex workers. STUDY DESIGN: We analyzed data on pregnancy and contraceptive use collected during the baseline visit of a randomized, prospective formative trial which assessed diaphragm and microbicide acceptability among sex workers. To be eligible, women could not be pregnant or planning pregnancy for the next 2 months. RESULTS: Women (N=192) from four cities (Antananarivo, Antsiranana, Mahajanga and Toamasina) reported a median of 10 sex acts per week. Fifty-two percent reported a prior unwanted pregnancy, 45% at least one induced abortion and 86% that preventing future pregnancy was moderately to very important. During the last sex act, 24% used a hormonal method, 36% used a male condom, 2% used a traditional method and 38% used no method. Nearly 30% of participants reported that pregnancy prevention was moderately or very important but used no contraception at last sex; these women were categorized as having "unmet need" for contraception. In multivariable binomial regression analyses, factors associated with unmet need included low knowledge of contraceptive effectiveness [age- and site-adjusted prevalence ratio (PR): 2.1; 95% confidence interval (CI): 1.4-3.0] and low self-efficacy to negotiate condom use (age- and site-adjusted PR: 2.0; 95% CI: 1.4-3.0). CONCLUSIONS: Among these women, prior unwanted pregnancy and induced abortion were common and preventing future pregnancy was important, yet gaps in contraceptive use were substantial. Contraceptive knowledge and self-efficacy should be improved to promote contraceptive use by sex workers.

Safety analysis of the diaphragm in combination with lubricant or acidifying microbicide gels: effects on markers of inflammation and innate immunity in cervicovaginal fluid.

OBJECTIVE: Diaphragms are being considered for use with vaginal microbicide gels to provide enhanced protection against sexually transmitted pathogens. The purpose of this study was to determine whether use of a diaphragm with microbicide or placebo gel causes cervicovaginal inflammation or perturbations in cervicovaginal immune defense. METHOD OF STUDY: Eighty-one non-pregnant women were randomized into three groups and instructed to use Milex (CooperSurgical, Inc., Trumbull, CT, USA)diaphragms overnight for 14 days in combination with one of the two acid-buffering microbicide gels [ACIDFORM (Instead Inc., La Jolla, CA, USA) or BufferGel(trade mark) (BG; ReProtect Inc., Baltimore, Maryland)] or placebo gel (K-Y Jelly); Personal Products Inc., Raritan, NJ, USA). Cervicovaginal lavages (CVLs) were performed prior to study entry and on days 8 and 16. Nine soluble mediators of vaginal inflammation or immune defense were measured in CVLs by Bio-Plex or ELISA. RESULTS: Use of diaphragms with placebo or microbicide gel was not associated with increased levels of inflammation markers. Concentrations of secretory leukocyte protease inhibitor (SLPI) were markedly reduced in the BG group. CONCLUSION: Daily use of a diaphragm with placebo or acidifying microbicide gel did not cause cervicovaginal inflammation. However, diaphragm/BG use was associated with markedly reduced levels of SLPI, an important mediator of innate immune defense. Further studies are warranted to establish the safety of diaphragm/microbicide gel combinations.

Vaginal microbicide and diaphragm use for sexually transmitted infection prevention: a randomized acceptability and feasibility study among high-risk women in Madagascar.

BACKGROUND: In preparation for a randomized controlled trial (RCT), we conducted a pilot RCT of the acceptability and feasibility of diaphragms and candidate vaginal microbicide for sexually transmitted infection prevention among high-risk women in Madagascar. METHODS: Participants were randomized to four arms: (1) diaphragm (worn continuously) with Acidform applied in the dome; (2) diaphragm (worn continuously) with placebo gel hydroxyethylcellulose (HEC) in the dome; (3) HEC applied intravaginally before sex; (4) Acidform applied intravaginally before sex. All women were given condoms. Participants were followed weekly for 4 weeks. We fit unadjusted negative binomial regression models with robust variance estimators to generate the proportion of sex acts with casual partners where condoms and experimental study products were used. RESULTS: Retention was 98% among 192 participants. Experimental product use with casual partners was high, reported in 85%, 91%, 74%, and 81% of sex acts for women in the Acidform-diaphragm, HEC-diaphragm, HEC-alone, and Acidform-alone arms, respectively. However, the proportion reporting product use during 100% of acts with casual partners over the full follow-up period was much lower: 28% to 29% in the gel-diaphragm arms and 6% to 10% in gel-alone arms. Women used condoms in 62% to 67% of sex acts with casual partners, depending on the randomization arm. Participants found diaphragms easy to insert (97%) and remove (96%). Acidform users (with or without the diaphragm) reported more genitourinary symptoms than HEC users (14% vs. 5% of visits). CONCLUSIONS: A sexually transmitted infection prevention RCT of candidate microbicide with and without the diaphragm appears acceptable and feasible in this population.

Phase I safety trial of two vaginal microbicide gels (Acidform or BufferGel) used with a diaphragm compared to KY jelly used with a diaphragm.

OBJECTIVES: To assess the safety and acceptability of 2 vaginal microbicide gels (Acidform and BufferGel) used with a diaphragm compared to KY Jelly used with a diaphragm among low-risk, sexually abstinent women. STUDY DESIGN: Eighty-one women enrolled in a randomized, masked, phase I safety study using a diaphragm with Acidform, BufferGel, or KY Jelly for 6 to 10 hours nightly for 14 nights. Physical examination, colposcopy, and lab studies were performed after 1 and 2 weeks of use. Diaries and questionnaires were used to assess user acceptability. RESULTS: Sixty-nine participants (85%) completed the study. Safety and acceptability appeared similar among the 3 study groups and no serious adverse events related to the study products were reported. Adverse events were mild and anticipated. CONCLUSIONS: Acidform and BufferGel compared to KY Jelly, when used with diaphragm daily for 14 days, appeared to be safe and acceptable in a small study of low-risk abstinent women.