Impact of LACTIN-V on genital immunology following standard bacterial vaginosis treatment: Results from a randomized placebo-controlled trial

Background: Bacterial vaginosis (BV) is associated with genital inflammation and enhanced HIV risk. In contrast, a vaginal microbiome predominated by Lactobacillus crispatus is associated with lower proinflammatory cytokine levels and reduced HIV risk. We investigated the genital immune impact of a L. crispatus-based live biothera-peutic (LACTIN-V), which was recently demonstrated to reduce BV recurrence following standard BV treatment (NCT02766023). Methods: In this pilot immune study, genital cytokine levels were assayed for 48 participants who reported near-perfect adherence to assigned treatment during the phase 2b randomized double-blind placebo-controlled trial of LACTIN-V to prevent BV recurrence. All participants received topical metronidazole for 5-days and were then randomized 2:1 to LACTIN-V or matched placebo for 11 weeks. Vaginal swabs were collected before and after metronidazole therapy, and then at 4-, 8-, 12-, and 24-weeks. Cytokines were assayed using the MSD multiplex platform. The primary comparison was the impact of LACTIN-V use on vaginal levels of IL-1a, the prototypic inflammatory cytokine elevated during BV. Results: Vaginal IL-1a levels fell promptly in all participants immediately following metronidazole treatment (3.319 vs. 2.832; p = 0.0055). While this reduction was sustained for at least 24 weeks among participants subsequently receiving LACTIN-V (n = 32), vaginal IL-1a levels rebounded to baseline levels by 24 weeks in the placebo arm (n = 16; t = -2.638, p = 0.012). At 24 weeks, L. crispatus CTV-05 was detected by PCR in 16 participants (50%) in the LACTIN-V arm and 0 participants (0%) in the placebo arm (p = 0.001). Conclusions: Treatment with LACTIN-V following standard antibiotic treatment of BV not only reduced BV recurrence and increased L. crispatus CTV-05 colonization, but also resulted in more sustained reductions in vaginal IL-1alevels. Given the link between genital proinflammatory cytokines and female HIV acquisition, LACTIN-V may represent a novel strategy to reduce HIV risk among women.