# Phase 2 placebo-controlled randomized trial of LACTIN-V (Lactobacillus crispatus CTV-05) among women at high risk of HIV acquisition in Durban, South Africa

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2022 · $331,258

## Abstract

ABSTRACT
The human vaginal microbiota has long been considered a factor impacting women’s risk for acquiring sexually
transmitted infections (STIs) including HIV, but the extent of this contribution and the underlying mechanisms
have not been well defined. The FRESH (Females Rising through Education, Support, and Health) cohort
consists of HIV-uninfected young South African women in a region where over 60% of 24 year old women are
HIV infected. In this population, we demonstrated that women with vaginal microbial communities dominated by
Lactobacillus crispatus had a 4-fold lower rate of HIV acquisition, reduced numbers of mucosal CD4+ T cells and
lower levels of genital tract proinflammatory cytokines compared with women with communities deficient in
Lactobacillus species. This common syndrome of vaginal dysbiosis, characterized by a diverse, non-
Lactobacillus dominant microbial community, is known as bacterial vaginosis (BV). Standard treatment with
antibiotics leads to a decrease in BV-associated microbes, but re-colonization with Lactobacillus species is often
slow, and recurrence of BV is common. Given the apparent protection from infections afforded by a Lactobacillus-
dominant vaginal microbiota, an intervention strategy using live biotherapeutic products (LBP) is a logical
approach. LACTIN-V, vaginally administered and containining the endogenous L. crispatus CTV-05 strain, has
shown excellent tolerability and close to 80% colonization in Phase 1 and 2a studies in the US. We propose a
Phase 2 randomized, placebo-controlled trial of LACTIN-V nested within the FRESH cohort. In 60 young South
African women with a non-Lactobacillus-dominant microbiota, we plan to assess whether this intervention a)
reduces proinflammatory cytokines and HIV target cells in the lower genital tract, b) leads to a persistent
Lactobacillus-dominant vaginal microbial community and c) is safe and acceptable in this population of young
women at high risk for HIV. The development of female-controlled HIV prevention methods is an urgent priority,
but significant challenges remain, such as adherence issues with current approaches and the need for
sustainable large scale distribution. The use of a safe LBP is an important paradigm shift in the development of
HIV prevention technologies. The FRESH / LACTIN-V project will provide critical data to assess if LACTIN-V
could have the potential to offer women a safe, effective, durable, self-renewing, coitally independent, multi-
purpose prevention product that promotes vaginal health and provides protection from HIV and potentially other
STIs.

## Key facts

- **NIH application ID:** 10488446
- **Project number:** 3R01HD098978-04S2
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** CRAIG R COHEN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $331,258
- **Award type:** 3
- **Project period:** 2019-06-12 → 2025-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10488446

## Citation

> US National Institutes of Health, RePORTER application 10488446, Phase 2 placebo-controlled randomized trial of LACTIN-V (Lactobacillus crispatus CTV-05) among women at high risk of HIV acquisition in Durban, South Africa (3R01HD098978-04S2). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10488446. Licensed CC0.

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