# HIV Genomic Aging Project in Oncology (HIV-GAP)

> **NIH NIH R01** · H. LEE MOFFITT CANCER CTR & RES INST · 2023 · $759,346

## Abstract

ABSTRACT. People with HIV (PWH) experience higher cancer mortality and increased likelihood of cancer
relapse after initial therapy compared to HIV-uninfected cancer patients. Our prior work demonstrated that these
HIV-associated cancer outcome disparities persist after accounting for known risk factors. A novel approach to
identify targetable drivers of the poor cancer outcomes experienced by PWH is urgently needed to improve
prognosis. We posit that cancer outcomes in PWH are negatively impacted by prolonged immune dysfunction
that results in accelerated biological aging. Biological aging can be quantified using genomic biomarkers, such
as DNA methylation translated into epigenetic clocks and presence of age-related clonal hematopoiesis (ARCH).
The overarching goal of this proposal is to compare biological age, measured using genomic biomarkers,
between cancer patients with versus without HIV and to quantify associations between measured biological age
with important clinical outcomes. Previous studies in PWH (without cancer) indicate that HIV-infected individuals
have higher biological age, calculated using blood-based epigenetic clocks, compared to their chronological age.
This accelerated aging was associated with increased mortality. ARCH has also been reportedly increased in
PWH. ARCH is characterized by acquired mutations that expand over time in blood cells. Accumulation of these
mutations is linked to increased inflammation and adverse outcomes. Data suggest that ARCH may be twice as
prevalent in PWH (without cancer) compared to HIV-uninfected persons. Thus, there is evidence for a link
between HIV and advanced genomic aging in PWH (without cancer), which warrants exploration in the context
of cancer. To preliminarily explore our hypothesis, we sequenced blood DNA from 30 solid tumor patients (15
PWH and 15 HIV-uninfected) matched on chronological age. Our preliminary data indicate that genomic aging
is more advanced in cancer patients with HIV. We observed significantly higher epigenetic-based biological age
in the PWH. We detected ARCH mutations in 3 PWH but 0 HIV-uninfected patients. The median survival in PWH
was only 2 years, compared to 9 years in HIV-uninfected patients; most striking was the <1-year median survival
in the PWH with ARCH. In this proposal, we will utilize an established protocol at Moffitt Cancer Center and
Huntsman Cancer Institute to prospectively collect biospecimens from 400 cancer patients (200 with and 200
without HIV). The investigation is timely and compelling given that cancer is now a leading cause of death in
PWH, and incidence is increasing. We propose the following aims: 1) Compare the biological age of cancer
patients with versus without HIV using epigenetic clocks; 2) Compare baseline prevalence and therapy-related
evolution of ARCH between cancer patients with and without HIV; and 3) Quantify the association between
genomic biomarkers of aging and clinical outcomes, including aging-related function...

## Key facts

- **NIH application ID:** 10687211
- **Project number:** 5R01CA268973-03
- **Recipient organization:** H. LEE MOFFITT CANCER CTR & RES INST
- **Principal Investigator:** Anna Coghill
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $759,346
- **Award type:** 5
- **Project period:** 2021-09-20 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10687211

## Citation

> US National Institutes of Health, RePORTER application 10687211, HIV Genomic Aging Project in Oncology (HIV-GAP) (5R01CA268973-03). Retrieved via AI Analytics 2026-06-11 from https://api.ai-analytics.org/grant/nih/10687211. Licensed CC0.

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