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

Heijden, Wouter A van der; Deuren, Rosanne C. van; Wijer, Lisa Van de; Munckhof, Inge C.L. van den; Steehouwer, Marloes; Riksen, Niels P.; Netea, Mihai G.; Mast, Quirijn de; Vandekerckhove, Linos; Voer, Richarda M. de; Ven, André J. van der; Hoischen, Alexander

doi:10.1093/infdis/jiab419

Cited by 20 publications

(26 citation statements)

References 32 publications

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“…IL-6, CRP, sCD14, sCD163) were not related to CHIP in a recent publication by van der Heijden et al [10], levels of von Willebrand factor and D-dimer were increased in CHIP carriers among PWH. The HIV reservoir, low nadir CD4 þ cell counts and an increased CD4 þ / CD8 þ T cell ratio were also related to CHIP prevalence in this study [10]. In the Swiss HIV Cohort study and the Atherosclerosis Risk in Communities study (ARIC), HIV was associated with a two-fold increase in CHIP prevalence, and there was a trend towards an association between CHIP and coronary artery disease in PWH [11].…”

Section: Clonal Haematopoiesis Of Indeterminate Potential and Cardiov...mentioning

confidence: 84%

“…Although levels of inflammation and monocyte activation in PWH (e.g. IL-6, CRP, sCD14, sCD163) were not related to CHIP in a recent publication by van der Heijden et al [10], levels of von Willebrand factor and D-dimer were increased in CHIP carriers among PWH. The HIV reservoir, low nadir CD4 þ cell counts and an increased CD4 þ / CD8 þ T cell ratio were also related to CHIP prevalence in this study [10].…”

Section: Clonal Haematopoiesis Of Indeterminate Potential and Cardiov...mentioning

confidence: 84%

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HIV and cardiovascular disease: the role of inflammation

Dirajlal-Fargo

Funderburg

2022

Current Opinion in HIV and AIDS

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Purpose of reviewHIV and antiretroviral therapy (ART) use are linked to an increased incidence of atherosclerotic cardiovascular disease (ASCVD). Immune activation persists in ART-treated people with HIV (PWH), and markers of inflammation (i.e. IL-6, C-reactive protein) predict mortality in this population. This review discusses underlying mechanisms that likely contribute to inflammation and the development of ASCVD in PWH.Recent findingsPersistent inflammation contributes to accelerated ASCVD in HIV and several new insights into the underlying immunologic mechanisms of chronic inflammation in PWH have been made (e.g. clonal haematopoiesis, trained immunity, lipidomics). We will also highlight potential pro-inflammatory mechanisms that may differ in vulnerable populations, including women, minorities and children.SummaryMechanistic studies into the drivers of chronic inflammation in PWH are ongoing and may aid in tailoring effective therapeutic strategies that can reduce ASCVD risk in this population. Focus should also include factors that lead to persistent disparities in HIV care and comorbidities, including sex as a biological factor and social determinants of health. It remains unclear whether ASCVD progression in HIV is driven by unique mediators (HIV itself, ART, immunodeficiency), or if it is an accelerated version of disease progression seen in the general population.

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Section: Clonal Haematopoiesis Of Indeterminate Potential and Cardiov...mentioning

confidence: 84%

Section: Clonal Haematopoiesis Of Indeterminate Potential and Cardiov...mentioning

confidence: 84%

HIV and cardiovascular disease: the role of inflammation

Dirajlal-Fargo

Funderburg

2022

Current Opinion in HIV and AIDS

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“…Among PHW on stable antiretroviral therapy, CHIP was associated with low CD4 nadir and increased residual HIV-1 transcriptional activity. 104 Similar to non-HIV studies, CHIP among people living with HIV was associated with a greater burden of subclinical coronary atherosclerosis. 105…”

Section: Risk Factors For Clonal Hematopoiesismentioning

confidence: 72%

Genomic Aging, Clonal Hematopoiesis, and Cardiovascular Disease

Natarajan

2023

ATVB

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Chronologic age is the dominant risk factor for coronary artery disease but the features of aging promoting coronary artery disease are poorly understood. Advances in human genetics and population-based genetic profiling of blood cells have uncovered the surprising role of age-related subclinical leukemogenic mutations in blood cells, termed “clonal hematopoiesis of indeterminate potential,” in coronary artery disease. Such mutations typically occur in DNMT3A , TET2 , ASXL1 , and JAK2 . Murine and human studies prioritize the role of key inflammatory pathways linking clonal hematopoiesis with coronary artery disease. Increasingly larger, longitudinal, multiomics analyses are enabling further dissection into mechanistic insights. These observations expand the genetic architecture of coronary artery disease, now linking hallmark features of hematologic neoplasia with a much more common cardiovascular condition. Implications of these studies include the prospect of novel precision medicine paradigms for coronary artery disease.

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“…Previous work identified an association between HIV and an increased frequency of CHIP, in which single base pair alterations occur primarily in myeloid driver genes [10][11][12][13]. However, CHIP and mCAs differentially impact protein products and gene expression, potentially explaining observed differences of association.…”

Section: Discussionmentioning

confidence: 99%

Mosaic chromosomal alterations detected in men living with HIV and the relationship to non-Hodgkin lymphoma

Lin

Khan

Zhou

et al. 2023

Aids

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Objectives: People with HIV (PWH) have an elevated risk of non-Hodgkin lymphoma (NHL) and other diseases. Studying clonal hematopoiesis (CH), the clonal expansion of mutated hematopoietic stem cells, could provide insights regarding elevated NHL risk.Design: Cohort analysis of participants in the Multicenter AIDS Cohort Study (N ¼ 5979).Methods: Mosaic chromosomal alterations (mCAs), a type of CH, were detected from genotyping array data using MoChA. We compared CH prevalence in men with HIV (MWH) to HIV-uninfected men using logistic regression, and among MWH, assessed the associations of CH with NHL incidence and overall mortality using Poisson regression.Results: Comparing MWH to HIV-uninfected men, we observed no difference in the frequency of autosomal mCAs (3.9% vs. 3.6%, P-value ¼ 0.09) or mosaic loss of the Y chromosome (mLOY) (1.4% vs. 2.9%, P-value ¼ 0.13). Autosomal mCAs involving copy-neutral loss of heterozygosity (CN-LOH) of chromosome 14q were more common in MWH. Among MWH, mCAs were not associated with subsequent NHL incidence (autosomal mCA P-value ¼ 0.65, mLOY P-value ¼ 0.48). However, two MWH with diffuse large B-cell lymphoma had overlapping CN-LOH mCAs on chromosome 19 spanning U2AF2 (involved in RNA splicing), and one MWH with Burkitt lymphoma had high-frequency mCAs involving chromosome 1 gain and chromosome 17 CN-LOH (cell fractions 22.1% and 25.0%, respectively). mCAs were not associated with mortality among MWH (autosomal mCA P-value ¼ 0.52, mLOY P-value ¼ 0.93). Conclusions:We found limited evidence for a relationship between HIV infection and mCAs. Although mCAs were not significantly associated with NHL, mCAs detected in several NHL cases indicate a need for further investigation.

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

Cited by 20 publications

References 32 publications

HIV and cardiovascular disease: the role of inflammation

HIV and cardiovascular disease: the role of inflammation

Genomic Aging, Clonal Hematopoiesis, and Cardiovascular Disease

Mosaic chromosomal alterations detected in men living with HIV and the relationship to non-Hodgkin lymphoma

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