Phase 2 Trial of LACTIN-V in Women at High Risk of HIV Acquisition

Inclusion Criteria

• FRESH study participant.
• Capable of reading and writing English or isiZulu and voluntarily provide written informed consent to participate in the study and comply with all study procedures
• HIV-negative
• Nugent score 4-10 on vaginal Gram stain
• Otherwise healthy women, 18-23 years of age on the day of enrolment
• Regular predictable menstrual cycles or amenorrhoeic for at least 3 months due to use of a long-acting progestin.
• Willing to complete 7-day course of oral metronidazole.
• Willing to be asked questions about personal medical health and sexual history
• Willing to apply study agent vaginally and comply with study examinations
• Willing to self-administer Study Product on dosing days that do not coincide with regular FRESH study visits.
• Agree to try to abstain from sexual intercourse 12 hours prior to study visits that include a gynaecological exam (Randomization Visit 3, Follow-up Visit 11, Final Visit 19).
• Agree to try to abstain from sexual intercourse for 12 hours after study product administration to ensure that the product will remain inside the vagina.
• Agree to abstain from the use of any other vaginal product throughout the trial period from the time of enrolment through the end of the study.

Note: Intravaginal products include contraceptive creams such as Gynol II, gels, foams, sponges, lubricants not approved by the study investigators, tampons and douches.

• Must be stable on a reliable method of long-acting birth control and agree to remain on, for the duration of the study (if of childbearing potential) or, of non-childbearing potential (permanently sterile).

Exclusion Criteria

• Urogenital infection (as tested during the FRESH Week 5 Study Visit, reported within 30 days of detection at the LACTIN-V Enrolment Visit).

Note: Urogenital infection includes urinary tract infection, Trichomonas (T.) vaginalis, Neisseria (N.) gonorrhoeae, Chlamydia (C.) trachomatis, Mycoplasma genitalium.

• Diagnosis of two or more outbreaks of N. gonorrhoeae, C. trachomatis, T. vaginalis, Mycoplasma genitalium, or herpes simplex virus (herpes genitalis) within 6 months prior to enrolment.
• Subject is ineligible if menstrual cycle length is less than 21 days
• Subject is ineligible if deep epithelial disruption is observed on genital examination noted on or before the Randomization Visit
• Positive for HIV (as tested during the FRESH Week 5 Study Visit, within 30 days of the LACTIN-V Enrolment Visit).
• Current pregnancy or within 2 months of last pregnancy
• Vaginal or systemic antibiotic or antifungal therapy within 21 days of enrolment
• Use of disulfiram within past 2 weeks or other contraindication to use of metronidazole
• Any condition requiring regular periodic use of systemic antibiotics during participation in the trial
• Investigational drug use other than LACTIN-V within 30 days or 10 half- lives of the drug, whichever is longer, of Enrolment Visit
• Other planned participation in an investigational drug study while participating in this study
• Intrauterine device (IUD) insertion or removal, pelvic surgery, cervical cryotherapy or cervical laser treatment within the last 2 months prior to enrolment
• Use of vaginal ring (e.g, NuvaRing) within 3 days of enrolment or during the course of the study
• Hysterectomy
• Unwilling to complete 7 days of oral metronidazole (twice daily) with the last dose taken no later than 48 hours prior to randomization (minimum of 12 of 14 doses required)
• Use of new long-acting hormonal treatments. Participant may be enrolled if stable (>1 month) on existing therapy as determined by the principal investigator (PI)
• Known allergy to any component of LACTIN-V/placebo or metronidazole or to nitroimidazole derivatives or latex (condoms)
• Any social, medical, or psychiatric condition including history of drug or alcohol abuse that in the opinion of the investigator would make it difficult for the participa