# Effects of Hormonal Contraceptives on Genital Immunity and HIV Susceptibility

> **NIH NIH R01** · UNIVERSITY OF WASHINGTON · 2020 · $566,902

## Abstract

ABSTRACT
An unanswered question of large public health importance for women living in settings with high HIV burden is
whether the use of any hormonal contraceptive method, and injectable depot medroxyprogesterone acetate
(DMPA) in particular, increases HIV risk. The objective of this proposal is to conduct biologic studies of the
potential mechanisms by which hormonal contraceptives may render women more susceptible to HIV infection.
A rigorous clinical trial, “ECHO,” to definitively address the question of HIV acquisition risk with the use of
contraceptives has just enrolled the first participants. In the trial, women are randomly assigned to use injectable
DMPA, the levonorgestrel (LNG) contraceptive implant, or the non-hormonal T-380 copper intrauterine
contraceptive device (IUD), equally effective contraceptive methods, positioning the trial to overcome many of
the challenges that have plagued prior observational studies. Through the proposed work, we will enroll a
comparable group of women using no contraception to serve as an additional control group. The trial does not
include provisions to collect genital samples or conduct mechanistic studies. This proposal seizes an
unprecedented opportunity to conduct studies nested within ECHO to test the most promising hypotheses about
mechanisms by which hormonal contraceptives may increase HIV risk, including that hormonal contraceptives
elicit: 1) increases in vaginal phylotypes associated with HIV risk, 2) increases in inflammation leading to HIV
target cell recruitment or activation, 3) increases in target cell homing pathways, and/or 4) disruptions in mucosal
barrier integrity. We will use state-of-the-art laboratory techniques – including qPCR, 16S rRNA sequencing, flow
cytometry, targeted and discovery mass spectrometry-based proteomics, and SmartSeq – to achieve the study
aims. The specific aims are to: 1) identify key vaginal phylotypes altered via initiation of hormonal contraceptives
(DMPA versus copper IUD, DMPA versus no contraception, DMPA versus LNG implant, etc.) that mediate
heightened susceptibility to HIV infection; 2) examine whether initiation of hormonal contraceptives elicits
increased genital inflammation and HIV target cells and whether this correlates with increased HIV risk; and 3)
determine whether initiation of hormonal contraceptives elicits increases in target cell homing pathways, as
measured by the vaginal transcriptome, and/or decreases in epithelial integrity, as measured by secreted
proteome, and whether these changes correlate with HIV infection. Finally, these large mucosal databases will
be integrated with data-driven computational modeling to generate testable hypotheses about pathways leading
to HIV infection. This study will identify mechanisms through which hormonal contraceptives alter genital
mucosa, and may identify molecular and cellular biomarkers of increased mucosal HIV susceptibility. Results
from this study will be pertinent for contraceptive reco...

## Key facts

- **NIH application ID:** 10006893
- **Project number:** 5R01HD089831-05
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** Renee A. Heffron
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $566,902
- **Award type:** 5
- **Project period:** 2016-09-27 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10006893

## Citation

> US National Institutes of Health, RePORTER application 10006893, Effects of Hormonal Contraceptives on Genital Immunity and HIV Susceptibility (5R01HD089831-05). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10006893. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*