# MicroRNA Predictors of HIV Risk in Reproductive Age Women

> **NIH NIH R01** · BRIGHAM AND WOMEN'S HOSPITAL · 2021 · $812,249

## Abstract

Current contraceptive options for women facing risk of HIV are limited. Despite evidence of increased risk of HIV
acquisition associated with progestin-only contraceptives, predominantly DMPA, millions of women around the
world continue using DMPA with an estimated >140 million using this or other hormonal contraceptives (HC).
Moreover, DMPA is the most common contraceptive method in sub-Saharan Africa – the region that bears an
estimated 70% of the global HIV-infection burden. Vaginal dysbiosis, another risk factor for HIV acquisition, is
also more common in women in this high HIV incidence region. Insights from our research gained in one of the
largest prospective cohorts designed to investigate the association between HC use and HIV acquisition (HC-
HIV study), support the following paradigms: 1) DMPA users develop aberrant cervical and systemic immunity
that precedes HIV seroconversion and 2) altered vaginal microbiota potentiates DMPA effects on cervical
immunity. The lack of understanding of the molecular mechanisms underlying the HC-immunity-microbiota
interactions leading to increased HIV susceptibility is limiting efforts to design safer contraceptive and preventive
technologies. We propose a novel hypothesis-driven paradigm to test the role of micro-RNAs (miRNAs) in risk
of HIV acquisition. Because of their stability in the circulation, ubiquitous gene silencing function, and emerging
evidence of important roles of small non-coding RNAs in controlling HIV infection, miRNAs are attractive novel
therapeutic and diagnostic targets. No information on miRNA expression in association with HC and abnormal
vaginal microbiota is currently available. To fill this gap in mechanistic understanding, we propose the following
aims: (1) Identify circulating aberrant miRNAs associated with risk of HIV-1 acquisition and innate immunity in
reproductive age women; (2) Identify hormonally regulated miRNAs predictive of HIV risk and immune imbalance
that precedes HIV seroconversion; (3) Identify miRNAs regulated by vaginal dysbiosis that may facilitate
communication between systemic and mucosal immunity imbalance associated with HIV risk. We will utilize
~1000 banked sera and cervicovaginal secretions from the longitudinal HC-HIV cohorts in Uganda and
Zimbabwe and four clinical trials conducted in the United States representing a racially diverse population.
Comprehensive demographic, clinical and laboratory information available on known major factors for HIV risk
in these cohorts will allow robust statistical modeling. We will use rigorous state-of-the-art technologies and
bioinformatics tools for transcriptomic, proteomic and functional genomics to generate profiles of differentially
expressed miRNAs and targeted genes and pathways with roles in the risk of HIV acquisition. This research
provides a unique opportunity to elucidate and validate the complex associations between endogenous and
exogenous hormones, bacterial vaginosis and HIV-1 through analysis...

## Key facts

- **NIH application ID:** 10129988
- **Project number:** 5R01HD099091-03
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** RAINA N. FICHOROVA
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $812,249
- **Award type:** 5
- **Project period:** 2019-05-13 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10129988

## Citation

> US National Institutes of Health, RePORTER application 10129988, MicroRNA Predictors of HIV Risk in Reproductive Age Women (5R01HD099091-03). Retrieved via AI Analytics 2026-06-11 from https://api.ai-analytics.org/grant/nih/10129988. Licensed CC0.

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