# Clonal Hematopoeisis in HIV and Aging

> **NIH NIH R21** · WEILL MEDICAL COLL OF CORNELL UNIV · 2020 · $211,875

## Abstract

Project Summary
Data support a higher prevalence of co-morbidities and accentuated or accelerated aging in people living with
HIV (PLWH), including a higher prevalence of frailty and physical disability. The potential role of clonal
hematopoiesis (CH) --the proliferation of hematopoetic stem cells with acquired mutations that confer a
competitive growth advantage-- in promoting inflammation and aging-related complications in PLWH is
unknown. While the prevalence of CH in the general population increases with age and is a potential pre-
malignant, pro-inflammatory state associated with cardiovascular disease and mortality, there is a major gap in
our knowledge about the prevalence and impact of CH in PLWH compared to controls without HIV. In a mouse
model, bacterial translocation across the gut barrier via compromised epithelial tight junctions of the
gastrointestinal tract causes endotoxin-responsive expansion of CH clones via toll-like receptor dependent
pathways. An analogous state of compromised intestinal integrity in chronic HIV infection may favor
expansion/persistence of CH clones. Our overarching hypothesis is that CH is more prevalent in PLWH and
contributes to accentuated/accelerated aging. We will use a multidisciplinary approach with correlative studies
in humans to address the following aims: 1) Test for the elevated prevalence and quantity of CH in PLWH
compared to matched controls without HIV; 2) Test for increased cognitive impairment, frailty, reduced physical
function, and inflammaging biomarkers in the presence of CH. We will use data and archived specimens from
500 participants age 55 and older living with HIV and an equal number without HIV from the Multicenter AIDS
Cohort Study-Women's Interagency HIV Study Combined Cohort Study. Controls without HIV will be matched
on age, race, and ethnicity. We will use targeted exome sequencing to detect CH mutations in blood using
>2% variant allele fraction as the threshold for CH detection as in our prior study in the general population. We
will measure a circulating biomarker of inflammation (interleukin-6), intestinal integrity, and bacterial
translocation from archived plasma specimens. Our novel, exploratory investigations will yield important data
to inform the design of more definitive human studies aimed at understanding the pathogenesis of aging-
related complications in PLWH and will enable future interventional studies.

## Key facts

- **NIH application ID:** 10013829
- **Project number:** 1R21AG066552-01A1
- **Recipient organization:** WEILL MEDICAL COLL OF CORNELL UNIV
- **Principal Investigator:** MARSHALL J GLESBY
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $211,875
- **Award type:** 1
- **Project period:** 2020-05-15 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10013829

## Citation

> US National Institutes of Health, RePORTER application 10013829, Clonal Hematopoeisis in HIV and Aging (1R21AG066552-01A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10013829. Licensed CC0.

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