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ObjectiveEvaluate safety of Ovaprene, an investigational non-hormonal vaginal contraceptive designed for monthly use.Study designOpen-label, multicenter study enrolling heterosexually-active women with previous permanent contraception who underwent assessments during five menstrual cycles: baseline postcoital test cycle, diaphragm postcoital test cycle, Ovaprene safety cycle, and two Ovaprene postcoital test cycles. Safety outcomes included treatment emergent adverse events (TEAEs), systemic laboratory findings, pelvic examinations, colposcopies, Nugent scores, determination of community state types of vaginal microbiota, and anti-Escherichia coli activity and inflammatory markers in cervicovaginal fluids.ResultsWe enrolled 38 participants. Of these, 33 used Ovaprene and completed 77 Ovaprene cycles. The most common product-related urogenital TEAEs were bacterial vaginosis (BV) and vaginal odor. The frequency of transitioning from Lactobacillus-dominated community state type to community state type IV (not Lactobacillus-dominated) was similar before Ovaprene use and afterwards. Mean Nugent scores were

Introduction: Globally, many young women face the overlapping burden of HIV infection and unintended pregnancy. Protection against both may benefit from safe and effective multipurpose prevention technologies. Methods: Healthy women ages 18-34 years, not pregnant, seronegative for HIV and hepatitis B surface antigen, not using hormonal contraception, and at low risk for HIV were randomized 2:2:1 to continuous use of a tenofovir/levonorgestrel (TFV/LNG), TFV, or placebo intravaginal ring (IVR). In addition to assessing genital and systemic safety, we determined TFV concentrations in plasma and cervicovaginal fluid (CVF) and LNG levels in serum using tandem liquid chromatography-mass spectrometry. We further evaluated TFV pharmacodynamics (PD) through ex vivo CVF activity against both human immunodeficiency virus (HIV)-1 and herpes simplex virus (HSV)-2, and LNG PD using cervical mucus quality markers and serum progesterone for ovulation inhibition. Results: Among 312 women screened, 27 were randomized to use one of the following IVRs: TFV/LNG (n = 11); TFV-only (n = 11); or placebo (n = 5). Most screening failures were due to vaginal infections. The median days of IVR use was 68 [interquartile range (IQR), 36-90]. Adverse events (AEs) were distributed similarly among the three arms. There were two non-product related AEs graded >2. No visible genital lesions were observed. Steady state geometric mean amount (ssGMA) of vaginal TFV was comparable in the TFV/LNG and TFV IVR groups, 43,988 ng/swab (95% CI, 31,232, 61,954) and 30337 ng/swab (95% CI, 18,152, 50,702), respectively. Plasma TFV steady state geometric mean concentration (ssGMC) was <10 ng/ml for both TFV IVRs. In vitro, CVF anti-HIV-1 activity showed increased HIV inhibition over baseline following TFV-eluting IVR use, from a median of 7.1% to 84.4% in TFV/LNG, 15.0% to 89.5% in TFV-only, and -27.1% to -20.1% in placebo participants. Similarly, anti-HSV-2 activity in CVF increased >50 fold after use of TFV-containing IVRs. LNG serum ssGMC was 241 pg/ml (95% CI 185, 314) with rapid rise after TFV/LNG IVR insertion and decline 24-hours post-removal (586 pg/ml [95% CI 473, 726] and 87 pg/ml [95% CI 64, 119], respectively). Conclusion: TFV/LNG and TFV-only IVRs were safe and well tolerated among Kenyan women. Pharmacokinetics and markers of protection against HIV-1, HSV-2, and unintended pregnancy suggest the potential for clinical efficacy of the multipurpose TFV/LNG IVR. [ABSTRACT FROM AUTHOR]

An abstract of the article "Assessment of the Vaginal Residence Time of Biomarkers of Semen Exposure" by Andrea R. Thurman, Terry A. Jacot, Johan Melendez and colleagues is presented.

Objective: To describe and compare systemic and local pharmacokinetics (PK) and cervicovaginal (CV) pharmacodynamics (PD) of oral tenofovir disoproxil fumarate (TDF) in combination with emtricitabine (FTC) with tenofovir (TFV) intravaginal ring (IVR)., Design: Phase I, randomized, parallel-group study. Women (n = 22) used TDF/FTC oral tablets daily or TFV IVR continuously and were assessed at baseline and 14 days., Methods: TFV and FTC concentrations were measured in plasma, CV fluid (CVF), and CV tissue. TFV-diphosphate and FTC-triphosphate were assessed in CV tissue. In vitro PD antiviral activities of TFV and FTC (using in vivo concentration ranges) were modeled in the CVF and by infecting CV tissue explants ex vivo with HIV-1BaL., Results: Adverse events (AEs) were more common with oral TDF/FTC use (P < 0.01). The median CVF TFV concentrations were 106 ng/mL after use of TFV IVR vs. 102 ng/mL for TDF/FTC. The median TFV and TFV-diphosphate concentrations in CV tissue were >100-fold higher among IVR users. The median CVF FTC concentrations were 103 ng/mL. FTC and FTC-triphosphate were detected in all CV tissues from TDF/FTC users. HIV inhibitory activity of CVF increased significantly with treatment in both cohorts (P < 0.01) but was higher in TFV IVR users (P < 0.01). In vitro inhibition of tissue infection with ex vivo administration of TFV and FTC was dose dependent, with maximal efficacy achieved with 10 µg/mL TFV, 1 µg/mL FTC, and 0.1 µg/mL of TFV and FTC combined., Conclusions: Both products were safe and increased mucosal HIV inhibitory activity. In addition to systemic protection, oral TDF/FTC displays a PK/PD profile compatible with CV mucosal antiviral activity. TFV IVR resulted in fewer AEs, lower TFV plasma concentrations, higher CVF and tissue TFV and TFV-DP concentrations, and greater anti-HIV activity in CVF., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc.)