Feasibility and safety of estrogen ring and/or probiotics for improving vaginal health in African/Caribbean/Black women: results from a prospective, randomized, open-label, phase I trial (CTN 308)


BACKGROUND: Vaginal inflammation, diminished Lactobacilluscolonization and increased microbiota diversity (dysbiosis) are associated with increased risk of HIV infection. Studies indicate that ~40% of African/Caribbean/Black (ACB) women have dysbiotic vaginal microbiota. To determine if probiotics and intravaginal estrogen are acceptable and safe interventions to improve vaginal health in pre-menopausal ACB women, a prospective, randomized, open-label, intervention phase I trial (CTN 308; NCT03837015) was conducted.
METHODS: Pre-menopausal ACB women aged 18-49 from the Toronto area were enrolled and baseline samples collected. Participants were randomized to: low dose intravaginal estradiol (Estringâ; 7.5mg/day), a twice daily vaginal probiotic (RepHreshä Pro-Bä; 1x107 cfu total of L. rhamnosusGR-1 and L. reuteri RC-14 per capsule), or a combination of oral or vaginal probiotic with Estring for 30 days. Participants returned a week after intervention for final assessment. Enrolment, retention, and intervention protocol (IP) adherence rates were calculated to assess trial feasibility. Adverse events (AEs) and blood markers were monitored to evaluate safety.
RESULTS: Between November 2019 and December 2021, 63 ACB women were screened, 51 (81%) enrolled, and 41 completed the study (80% retention of enrolled). Enrolment and retention rates met or exceeded targets of 70% and 80%, respectively. During the study, 6 (12%) participants withdrew consent, 4 (8%) withdrew due to IP non-compliance, and 1 (2%) was lost to follow up. Of those that completed the study, IP adherence was high among all treatment groups, with an overall Estring adherence rate of 94% (12% SD, IQR 93%-100%) and an overall probiotic adherence rate of 91% (13% SD, IQR 87%-100%). A total of 92 AEs were reported by 29 (57%) participants, 66 (72%) of which were mild in intensity and 86 (93%) resolved by the end of the study. No severe AEs were reported, and no clinically significant blood marker changes were observed.
CONCLUSIONS: Enrolment, retention and adherence rates demonstrate low dose intravaginal estrogen and/or twice daily probiotics are well tolerated interventions. Most AEs were mild and short-term, and no severe AEs occurred. Overall, administration of intravaginal estrogen and/or twice daily probiotics are safe, acceptable interventions. Analysis of biological samples will determine whether interventions augmented vaginal Lactobacillus colonization.

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