CTN 308: Estrogen and Probiotic Treatment for Vaginal Health

About the Study

This pilot trial compared the effects of low-dose estrogen, a probiotic, or both, in improving the type of bacteria living in the vagina and decreasing the risk of HIV infection in pre-menopausal women.

Background

The risk of HIV acquisition in women is roughly double that of men, due in part to a risk of inflammation in the female genital tract. Susceptibility to sexual transmission of infections, such as HIV, can be affected by different levels and types of various naturally occurring bacteria known as vaginal microbiota. The hormone estrogen is thought to encourage the development of a protective type of bacteria (Lactobacilli) and decrease inflammation. There are also other vaginal microbes that may increase HIV susceptibility. These may be more common in Black and Hispanic women compared to White and Asian women.

CTN 308 assessed whether a protective vaginal microbiota can be developed in African, Caribbean, and Black (ACB) women who have flora that may put them at a greater susceptibility to HIV infection.

Study Approach

This study enrolled 50 ACB women from the Greater Toronto Area. Participants were randomized to receive a 30-day course of one of the following treatments:

• A low-dose estrogen vaginal ring
• A low-dose estrogen vaginal ring with a vaginal probiotic
• A low-dose estrogen vaginal ring with an oral probiotic
• A vaginal probiotic alone

Participants gave blood and cervical/vaginal swabs for testing at baseline, during the study, and after completion of treatment. Participants were also asked to take vaginal swabs at home. Swabs were tested for microbial levels and types.

As a pilot study, CTN 308 was primarily focused on the safety and tolerability of these treatments in combination. The team also investigated changes in vaginal health and inflammation as an indicator of HIV susceptibility.

Results

The majority of participants were born outside of Canada and immigrated during adulthood. The average age across study groups was 35. Forty-one participants (82%) were retained until the end of the study. Adherence to the study interventions was high (93%). Some mild adverse events were noted, most of which were resolved by the end of the study. Levels of lactobacillus, a protective type of bacteria, increased over the course of the study in participants who received a vaginal probiotic (either with or without a low-dose estrogen ring). In these participants, researchers noted a consistent decrease in inflammation at the end of the study.

Conclusion

The interventions used in this study were safe and well tolerated. This pilot study showed that participants are willing and able to adhere to the treatments and stay in the study. The results also suggest that interventions that directly target the vaginal microbiome could be effective in reducing inflammation.

The research team presented their results and consulted with the community in a public event in collaboration with Women’s Health in Women’s Hands Community Health Centre. After a strong community response and the supporting evidence from the CTN 308 pilot trial, the team has now designed a larger trial to directly test the potential of these interventions to reduce bacteria-related vaginal inflammation, which increases HIV risk.