# Changes in Enteric Microbiota and Inflammation with HIV PrEP

> **NIH NIH K08** · SEATTLE CHILDREN'S HOSPITAL · 2024 · $193,540

## Abstract

PROJECT SUMMARY/ABSTRACT
Although HIV remains a major global health problem, strategies such as Pre-Exposure Prophylaxis (PrEP) can
reduce the incidence of new infections. However, the antiretrovirals used for HIV prevention have been
associated with increased enteric inflammation in individuals using them. We hypothesize that their broad activity
affects both the viral and bacterial communities of the gut, causing local inflammation which may cause epithelial
dysfunction and increase microbial translocation and systemic inflammation.
We propose a series of metagenomic experiments to characterize the inflammatory contributions of intestinal
viruses and bacteria and their changes with PrEP. For this novel research, we must first enroll a cohort of
participants starting HIV PrEP and a similar group of control participants not using PrEP. We will collect blood
and stool samples at baseline and after three months. First, we will characterize the virome fromstool specimens
using metagenomic sequencing of filtered viral particles and compare the changes of within- and between-
individual diversity in the participants on PrEP and those in the control group (aim 1). Next, we will use
metagenomic sequencing to characterize stool bacterial populations, including prophages (aim 2). We will
computationally predict bacterial targets of bacteriophages, then culture the identified virus-bacterial pairs from
participant specimens. Using these cultures, we will validate the predicted interactions and assess the ability of
PrEP to disrupt them. Finally, we will measure inflammatory markers in stool and blood and use the viral and
bacterial abundances to identify which organisms are most strongly associated with inflammation (aim 3). These
experiments will identify viruses and bacteria which interact with each other and with PrEP and define their
impact on host inflammation.
Dr. Maust’s career development plan builds on his background in computational biology, and lab expertise in
analyzing bacterial communities by marker gene sequencing and adds training in metagenomic sequencing,
biostatistical techniques, and methods for viral and bacterial culture. This K08 award is a well-structured way for
him to make maximal use of UW and Seattle Children’s extensive scientific resources to achieve independence
as a physician scientist, advancing his career goal to understand microbial interactions as they impact host
immunity to guide therapeutic interventions.

## Key facts

- **NIH application ID:** 10913543
- **Project number:** 5K08AI177080-02
- **Recipient organization:** SEATTLE CHILDREN'S HOSPITAL
- **Principal Investigator:** Brandon Swartz Maust
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $193,540
- **Award type:** 5
- **Project period:** 2023-09-01 → 2028-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10913543

## Citation

> US National Institutes of Health, RePORTER application 10913543, Changes in Enteric Microbiota and Inflammation with HIV PrEP (5K08AI177080-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10913543. Licensed CC0.

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