# Frailty, HIV Infection, Injection Drug Use and the Inflammatory-Microbiome

> **NIH NIH R01** · JOHNS HOPKINS UNIVERSITY · 2021 · $676,074

## Abstract

PROJECT SUMMARY/ABSTRACT
With effective antiretroviral therapy (ART), life expectancy for HIV-infected persons has markedly improved, yet
marked deficits in survival remain for HIV-infected persons with a history of injecting drugs (PWID). Disparities
among PWID have been attributed in part to a shifting spectrum of disease to aging-associated conditions
driven by persistent inflammation even with ART. Frailty is an important aging-related state of vulnerability to
stress, with an increased burden in HIV infection, strongly associated with heightened inflammation, and
predictive of premature mortality and aging-related morbidity among PWID. Injecting drugs itself can increase
the severity of inflammation in HIV. The human gut microbial ecosystem (gut microbiome) critically regulates
inflammation and immunity. Alterations in the gut microbiome (gut dysbiosis) together with associated
disruptions of gut structure and immune integrity constitute an inflammatory-microbiome signature (gut
dysbiosis, increased gut permeability, translocation of microbial products, immune activation, heightened
inflammation) linked to adverse aging-associated inflammatory conditions and disease. Proposed is a
systematic investigation of the role of HIV infection and injection drug use (IDU) in defining the inflammatory-
microbiome signature and determination of the relationship of this signature to frailty. Through assessments of
the fecal and mucosal microbiome in the AIDS Linked to the IntraVenous Experience (ALIVE) cohort of HIV-
infected and epidemiologically comparable HIV-uninfected PWID, we will determine how HIV infection and
active IDU alter microbiome composition and function and the relationship of these changes to inflammation
and frailty progression over time. Using a germ free murine model, we will further define the frail human
microbial communities and gene products that precipitate inflammation. These studies will facilitate elucidation
of gut microbial determinants of frailty among HIV-infected PWID and could significantly inform microbiota
modulation strategies to reduce frailty-associated inflammation beyond ART. Understanding the role of the gut
microbiome in relation to HIV, injection drug use, and frailty remains a critical next step to reducing the marked
disparities in clinical outcomes among HIV-infected PWID.

## Key facts

- **NIH application ID:** 9967969
- **Project number:** 5R01AG060825-03
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Damani Piggott
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $676,074
- **Award type:** 5
- **Project period:** 2018-09-30 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9967969

## Citation

> US National Institutes of Health, RePORTER application 9967969, Frailty, HIV Infection, Injection Drug Use and the Inflammatory-Microbiome (5R01AG060825-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9967969. Licensed CC0.

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