Increased CHIP Prevalence Amongst People Living with HIV.

Bick, Alexander G; Popadin, Konstantin; Thorball, Christian W; Uddin, Md Mesbah; Zanni, Markella; Yu, Bing; Cavassini, Matthias; Rauch, Andri; Tarr, Philip; Schmid, Patrick; Bernasconi, Enos; Gunthard, Huldrych; Libby, Peter; Boerwinkle, Eric; McLaren, Paul; Ballantyne, Christie M; Grinspoon, Steven K; Natarajan, Pradeep; Fellay, Jacques (7 November 2020). Increased CHIP Prevalence Amongst People Living with HIV. (medRxiv). Cold Spring Harbor Laboratory 10.1101/2020.11.06.20225607

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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.

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