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Increased CHIP Prevalence Amongst People Living with HIV.

TitleIncreased CHIP Prevalence Amongst People Living with HIV.
Publication TypeJournal Article
Year of Publication2020
AuthorsBick AG, Popadin K, Thorball CW, Uddin MMesbah, Zanni M, Yu B, Cavassini M, Rauch A, Tarr P, Schmid P, Bernasconi E, Gunthard H, Libby P, Boerwinkle E, McLaren P, Ballantyne CM, Grinspoon SK, Natarajan P, Fellay J
JournalmedRxiv
Date Published2020 Nov 07
Abstract

People living with human immunodeficiency virus (PLWH) have significantly increased risk for cardiovascular disease in part due to inflammation and immune dysregulation. Clonal hematopoiesis of indeterminate potential (CHIP), the age-related acquisition and expansion of hematopoietic stem cells due to leukemogenic driver mutations, increases risk for both hematologic malignancy and coronary artery disease (CAD). Since increased inflammation is hypothesized to be both a cause and consequence of CHIP, we hypothesized that PLWH have a greater prevalence of CHIP. We searched for CHIP in multi-ethnic cases from the Swiss HIV Cohort Study (SHCS, n=600) and controls from the Atherosclerosis Risk in the Communities study (ARIC, n=8,111) from blood DNA-derived exome sequences. We observed that HIV is associated with increased CHIP prevalence, both in the whole study population and in a subset of 230 cases and 1002 matched controls selected by propensity matching to control for demographic imbalances (SHCS 7%, ARIC 3%, p=0.005). Additionally, unlike in ARIC, ASXL1 was the most commonly implicated mutated CHIP gene. We propose that CHIP may be one mechanism through which PLWH are at increased risk for CAD. Larger prospective studies should evaluate the hypothesis that CHIP contributes to the excess cardiovascular risk in PLWH.

DOI10.1101/2020.11.06.20225607
Alternate JournalmedRxiv
PubMed ID33173934
PubMed Central IDPMC7654930
Grant ListRC2 HL102419 / HL / NHLBI NIH HHS / United States
P30 DK040561 / DK / NIDDK NIH HHS / United States
DP5 OD029586 / OD / NIH HHS / United States
R01 HL151283 / HL / NHLBI NIH HHS / United States
R01 HL148565 / HL / NHLBI NIH HHS / United States
U54 HG003273 / HG / NHGRI NIH HHS / United States
HHSN268201700002C / HL / NHLBI NIH HHS / United States
HHSN268201700001I / HL / NHLBI NIH HHS / United States
HHSN268201700004I / HL / NHLBI NIH HHS / United States
HHSN268201700004C / HL / NHLBI NIH HHS / United States
R01 HL134892 / HL / NHLBI NIH HHS / United States
R01 HL086694 / HL / NHLBI NIH HHS / United States
HHSN268201700005C / HL / NHLBI NIH HHS / United States
HHSN268201700001C / HL / NHLBI NIH HHS / United States
HHSN268201700003C / HL / NHLBI NIH HHS / United States
U01 HL123336 / HL / NHLBI NIH HHS / United States
HHSN268201700002I / HL / NHLBI NIH HHS / United States
HHSN268201700005I / HL / NHLBI NIH HHS / United States
HHSN268201700003I / HL / NHLBI NIH HHS / United States
R01 HL148050 / HL / NHLBI NIH HHS / United States