Clonal Hematopoiesis Is Associated With Low CD4 Nadir and Increased Residual HIV Transcriptional Activity in Virally Suppressed Individuals With HIV

Author:

van der Heijden Wouter A12ORCID,van Deuren Rosanne C134,van de Wijer Lisa12,van den Munckhof Inge C L13,Steehouwer Marloes34,Riksen Niels P13,Netea Mihai G135,de Mast Quirijn12,Vandekerckhove Linos6,de Voer Richarda M34,van der Ven Andre J12,Hoischen Alexander134

Affiliation:

1. Department of Internal Medicine, Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, the Netherlands

2. Radboud Institute for Health Sciences, Radboud University Medical Center, Nijmegen, the Netherlands

3. Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, the Netherlands

4. Department of Human Genetics, Radboud University Medical Center, Nijmegen, the Netherlands

5. Department for Genomics and Immunoregulation, Life and Medical Sciences Institute, University of Bonn, Bonn, Germany

6. HIV Cure Research Center, Department of Internal Medicine and Pediatrics, Faculty of Medicine and Health Sciences, Ghent University and Ghent University Hospital, Ghent, Belgium

Abstract

Abstract Clonal hematopoiesis, a common age-related phenomenon marked by expansion of cells with clonal hematopoiesis driver mutations, has been associated with all-cause mortality, cancer, and cardiovascular disease. People with HIV (PWH) are at risk for non-AIDS–related comorbidities such as atherosclerotic cardiovascular disease and cancer. In a cross-sectional cohort study, we compared clonal hematopoiesis prevalence in PWH on stable antiretroviral therapy with prevalence in a cohort of overweight individuals and a cohort of age- and sex-matched population controls. The prevalence of clonal hematopoiesis adjusted for age was increased and clone size was larger in PWH compared to population controls. Clonal hematopoiesis is associated with low CD4 nadir, increased residual HIV-1 transcriptional activity, and coagulation factors in PWH. Future studies on the effect of clonal hematopoiesis on the HIV reservoir and non-AIDS–related comorbidities are warranted.

Funder

AIDS Fonds Netherlands

ViiV Healthcare

Netherlands Organization for Scientific Research

European Research Council

European Union

Publisher

Oxford University Press (OUP)

Subject

Infectious Diseases,Immunology and Allergy

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