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To estimate contraceptive efficacy, safety, acceptability, and fit of a single-size diaphragm used with contraceptive gel.We conducted a multicenter trial in which 450 couples used the single-size diaphragm, 300 randomized to acid-buffering gel and 150 to nonoxynol-9, for at least 190 days and six menstrual cycles. Visits were at enrollment and after menstrual cycles 1, 3, and 6. Study outcomes included pregnancy probability, safety, acceptability, and fit. Pregnancy and safety were compared with an historical control group who used a standard diaphragm with these gels.Most (439/450 [98%]) women could be fitted with the single-size diaphragm. A total of 421 of 450 (94%) provided follow-up. The 35 study pregnancies yielded 6-month Kaplan-Meier cumulative typical use pregnancy probabilities per 100 women with 95% confidence intervals (CIs) of 10.4 (6.9-14.0) for all users and 9.6 (5.5-13.6) and 12.5 (5.4-19.5) with acid-buffering gel and nonoxynol-9, respectively. Historical control analysis yielded a propensity score-adjusted estimate of this pregnancy probability for the single-size diaphragm of 11.3 compared with 10.7 per 100 women for the standard diaphragm ([rounded] difference 0.7, 95% CI -3.6 to 4.9). Approximately half (51%) reported at least one urogenital event but compared favorably to the standard diaphragm in historical control analysis. Most (282/342 [82%]) liked the diaphragm. Results suggest that if provided by a clinician, 94% (95% CI 92-96%) could insert, correctly position, and remove the diaphragm.The single-size diaphragm was safe, as effective as a standard diaphragm, and acceptable when used with contraceptive gel.ClinicalTrials.gov, www.clinicaltrials.gov, NCT00578877.

Several microbicides, including nonoxynol-9 (N-9) and cellulose sulfate (CS), looked promising during early trials but failed in efficacy trials. We aimed to identify Phase I mucosal safety endpoints that might explain that failure. In a blinded, randomized, parallel trial, 60 healthy premenopausal sexually abstinent women applied Universal HEC placebo, 6% CS or 4% N-9 gel twice daily for 13½ days. Endpoints included immune biomarkers in cervicovaginal lavage (CVL) and endocervical cytobrushes, inflammatory infiltrates in vaginal biopsies, epithelial integrity by naked eye, colposcopy, and histology, CVL anti-HIV activity, vaginal microflora, pH, and adverse events. Twenty women enrolled per group. Soluble/cellular markers were similar with CS and placebo, except secretory leukocyte protease inhibitor (SLPI) levels decreased in CVL, and CD3(+) and CD45(+) cells increased in biopsies after CS use. Increases in interleukin (IL)-8, IL-1, IL-1RA, and myeloperoxidase (MPO) and decreases in SLPI were significant with N-9. CVL anti-HIV activity was significantly higher during CS use compared to N-9 or placebo. CS users tended to have a higher prevalence of intermediate Nugent score, Escherichia coli, and Enterococcus and fewer gram-negative rods. Most Nugent scores diagnostic for bacterial vaginosis were in N-9 users. All cases of histological inflammation or deep epithelial disruption occurred in N-9 users. While the surfactant N-9 showed obvious biochemical and histological signs of inflammation, more subtle changes, including depression of SLPI, tissue influx of CD45(+) and CD3(+) cells, and subclinical microflora shifts were associated with CS use and may help to explain the clinical failure of nonsurfactant microbicides.

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.