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HIV Genomic Aging Project in Oncology (HIV-GAP)

Award Number: R01CA268973
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/20/2021
PERIOD OF PERFORMANCE END DATE: 08/31/2026

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HIV Genomic Aging Project in Oncology (HIV-GAP) - 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 functional assessments. This study will address the critical knowledge gap of whether cancer patients with HIV are biologically older than age- matched cancer patients without HIV, and whether this advanced aging contributes to poor cancer outcomes.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2024 ( Subtotal = $761,817 )
2024	2024	H. LEE MOFFITT CANCER CENTER AND RESEARCH INSTITUTE HOSPITAL, INC.	12902 USF MAGNOLIA DR	TAMPA	FL	33612	HILLSBOROUGH	USA	Cancer Treatment Research	000	4	8/2/2024	NON-COMPETING CONTINUATION	$761,817
														Subtotal = $761,817

Issue Date FY: 2023 ( Subtotal = $759,346 )
2023	2023	H. LEE MOFFITT CANCER CENTER AND RESEARCH INSTITUTE HOSPITAL, INC.	12902 MAGNOLIA DR	TAMPA	FL	33612	HILLSBOROUGH	USA	Cancer Treatment Research	000	3	8/7/2023	NON-COMPETING CONTINUATION	$759,346
														Subtotal = $759,346

Issue Date FY: 2022 ( Subtotal = $757,699 )
2022	2022	H. LEE MOFFITT CANCER CENTER AND RESEARCH INSTITUTE HOSPITAL, INC.	12902 MAGNOLIA DR	TAMPA	FL	33612	HILLSBOROUGH	USA	Cancer Treatment Research	001	2	8/19/2022	NON-COMPETING CONTINUATION	$757,699
2022	2021	H. LEE MOFFITT CANCER CENTER AND RESEARCH INSTITUTE HOSPITAL, INC.	12902 MAGNOLIA DR	TAMPA	FL	33612	HILLSBOROUGH	USA	Cancer Treatment Research	000	1	11/17/2021	NEW	$0
														Subtotal = $757,699

Issue Date FY: 2021 ( Subtotal = $778,598 )
2021	2021	H. LEE MOFFITT CANCER CENTER AND RESEARCH INSTITUTE HOSPITAL, INC.	12902 MAGNOLIA DR	TAMPA	FL	33612	HILLSBOROUGH	USA	Cancer Treatment Research	000	1	9/20/2021	NEW	$778,598
														Subtotal = $778,598

Grand Total All Awards = $3,057,460

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HIV Genomic Aging Project in Oncology (HIV-GAP)

Award Number: R01CA268973

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 09/20/2021

PERIOD OF PERFORMANCE END DATE: 08/31/2026

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