Results from the first South African Health Products Regulatory Authority-approved randomised trial evaluating supplementation of standard antibiotic therapy with a commercially available probiotic in South African women with bacterial vaginosis

Background: Bacterial vaginosis (BV) increases HIV risk and adverse reproductive outcomes in women. The standard-of-care (SOC) for BV is antibiotic treatment; however, cure rates are low and recurrence frequent. In South Africa, no trial comparing probiotics to SOC for BV has been approved by the South African Health Products regulatory Authority (SAHPRA). We aimed to explore the South African regulatory and ethics environment to evaluate adjunctive probiotics for improvement of BV treatment in a randomized single-blinded trial of a locally sourced oral-vaginal-combination probiotic for vaginal health. Methods: South African women with symptomatic vaginal discharge were screened for BV and sexually transmitted infections (STIs) including Trichomonas vaginalis, Mycoplasma genitalium, Neisseria gonorrhoae and Chlamydia trachomatis. BV positive (by Nugent Scoring) STI negative women were randomized to Metrogel alone (n=12) or Metrogel followed by a commercially available South African oral/vaginal probiotic (n=18). BV cure at one month was the primary endpoint. Secondary endpoints were recurrence, symptoms, vaginal microbiota and genital inflammation over five months post-treatment, and acceptability of the administered probiotic. Results: SAHPRA reviewed and acknowledged this trial. Overall, 44.8% of women cleared BV one month post-treatment. Despite confirmed viability of probiotic species contained in the commercial oral/vaginal probiotic, they did not appear to colonize the female genital tract of most women in the intervention group. No significant differences in BV cure rates, vaginal pH, microbiota nor IL-1alpha concentrations were found between SOC and intervention groups, although we were underpowered to detect small differences. Acceptability and adherence to the probiotic product was high. Conclusion: Navigation of the SAHPRA registration process for evaluating a commercial probiotic in a randomised trial has laid the path for future trials of improved probiotic products for vaginal health in South Africa with adequate sample sizes. Acceptability of vaginally applied probiotics was high in South African women. Improvements in both the content and delivery of commercially available probiotic products for vaginal health should be considered.