Bacterial vaginosis is inflammation caused by an overgrowth of microorganisms that normally populate a woman’s vagina. While it can be cured with antibiotics, achieving a durable cure is difficult, as bacterial vaginosis often recurs after antibiotic treatments are completed. In findings published in The New England Journal of Medicine, researchers describe results of a Phase 2B clinical trial in which women applied LACTIN-V, comprised of live beneficial bacteria, following antibiotic treatment for bacterial vaginosis (BV). In the study, the experimental treatment was safe and significantly reduced the rate of BV recurrence. The study was conducted by researchers from the Sexually Transmitted Infections Clinical Trials Group supported by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health.
BV is the most common cause of vaginal symptoms among women in the United States, with an estimated prevalence of 29 percent in women ages 14 to 49, according to the Centers for Disease Control and Prevention. While not all BV cases are symptomatic, BV may be uncomfortable or painful and can increase the risk of contracting HIV or other sexually transmitted infections (STIs). In pregnant women, BV also is associated with higher rates of premature birth and low birth weight babies. BV can be difficult to cure: 20 to 75 percent of women with BV relapse within three months of receiving a standard five-day course of antibiotics.
LACTIN-V is designed to repopulate a depleted vaginal microbiome with Lactobacillus crispatus bacteria, common in the vaginas of healthy women. The paper’s authors hypothesized that this treatment could prevent more harmful bacteria from establishing colonies and causing BV. Early trials of LACTIN-V successfully used a dissolvable vaginal capsule to deliver L. crispatus. The researchers proposed that use of specialized vaginal applicators to deliver live L. crispatus may lead to higher and more sustained rates of bacterial colonization.
The trial enrolled 228 women who were diagnosed with BV but tested negative for STIs. Participants received a five-day vaginal course of metronidazole antibiotic gel to treat BV. They then returned to the clinic and were randomly assigned to receive either applicators containing LACTIN-V (152 volunteers) or placebo applicators without any live biotherapeutic (76 volunteers). Both groups were instructed to use the applicators five times during the first week and then twice weekly for 10 weeks. Researchers took vaginal swabs to track bacteria in the volunteers’ microbiomes, examined the used applicators, and performed additional STI tests, if necessary, at follow-up visits after 4, 8, 12 and 24 weeks.
After 12 weeks, volunteers who received LACTIN-V had significantly fewer recurrences of BV (30 percent) than volunteers who received placebo (45 percent). After 24 weeks, 39 percent of volunteers who received LACTIN-V experienced recurring BV, while 54 percent of patients who did not receive LACTIN-V experienced a recurrence. 79 percent of the women who received LACTIN-V were colonized with detectable levels of the L. crispatus bacteria at 12 weeks, while 48 percent were colonized at 24 weeks. More than 75 percent of volunteers in both arms of the study followed the dosing regimen.
While these results are promising, a Phase 3 trial to confirm the results is warranted, the researchers note. They also want to investigate whether LACTIN-V use can reduce risk of STIs and premature birth.
The research was supported by NIAID contracts HHSN272201300014I and HHSN27200007. For more information about the study, see NCT02766023 at Clinicaltrials.gov.
Cohen et al. Randomized Trial of Lactin-V to Prevent Recurrence of Bacterial Vaginosis. The New England Journal of Medicine DOI: 10.1056/NEJMoa1915254 (2020).