Effect of Clonal Hematopoiesis on Cardiovascular Disease in People Living with HIV

Wiley, Brian J.; Parsons, Tyler; Burkart, Samantha; Young, Andrew L.; Erlandson, Kristine M.; Tassiopoulos, Katherine; Wu, Kun; Gurnett, Christina A.; Presti, Rachel; Bolton, Kelly L.; Challen, Grant A.

doi:10.1016/j.exphem.2022.07.304

Cited by 9 publications

(8 citation statements)

References 17 publications

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“…In contrast to previous findings in murine models and in both PWH and uninfected [8,31,35], we did not find evidence of more CAD among participants with CHIP compared with participants without mutations, and this did not change after adjustment for smoking and other possible confounders. Our sample size was small, however, and the lack of association may be because of insufficient power although other studies with comparable sample sizes have found an association [8,9]. However, the association between CHIP and CAD is not consistently found across studies, and a recent UK biobank study found no association between clonal hematopoiesis and CAD in 200 453 individuals [36].…”

Section: Discussionmentioning

confidence: 72%

“…CHIP has been found to be more prevalent among PWH compared with uninfected individuals [8,[10][11][12]. In PWH, CHIP has been associated with an almost four-fold higher odds of cardiovascular events, and a variant allele fraction at least 1% has been associated with more than 50% coronary stenosis [8,9]. CHIP is strongly related to traditional risk factors including ageing and smoking but seems to be more prevalent in PWH even after controlling demographic risk factors [8,[10][11][12].…”

Section: Introductionmentioning

confidence: 99%

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Clonal hematopoiesis of indeterminate potential in persons with HIV

Knudsen,

Eskelund,

Benfield

et al. 2023

Aids

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Background: Clonal hematopoiesis of indeterminate potential (CHIP) has been associated with older age, inflammation and with risk of coronary artery disease (CAD). We aimed to characterize the burden of CHIP, and to explore the association between CHIP, inflammatory markers, and CAD in older persons living with HIV (PLWH). Methods: From the Copenhagen Comorbidity in HIV Infection (COCOMO) study, we included 190 individuals older than 55 years of age. We defined CHIP as variant allele fraction ≥ 2%. CAD was categorized according to the most severe coronary artery lesion on coronary CT angiography as 1) no coronary atherosclerosis; 2) any atherosclerosis defined as ≥1% stenosis, and 3) obstructive CAD defined as ≥50% stenosis. Results: In the entire population (median age 66 years, 87% men), we identified a total of 62 mutations distributed among 49 (26%) participants. The three most mutated genes were DNMT3A, TET2, and ASXL1, accounting for 49%, 25%, and 16% of mutations, respectively. Age and sex were the only variables associated with CHIP. IL-1β, IL-1Ra, IL-2, IL-6, IL-10, soluble CD14, soluble CD163 and TNF-α were not associated with CHIP and CHIP was not associated with any atherosclerosis or with obstructive CAD in adjusted analyses. Conclusions: In older, well-treated, Scandinavian PLWH, more than one in four had at least one CHIP mutation. We did not find evidence of an association between CHIP and inflammatory markers or between CHIP and CAD. CHIP is an unlikely underlying mechanism to explain the association between inflammation and CAD in treated HIV disease.

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Section: Discussionmentioning

confidence: 72%

Section: Introductionmentioning

confidence: 99%

Clonal hematopoiesis of indeterminate potential in persons with HIV

Knudsen,

Eskelund,

Benfield

et al. 2023

Aids

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“…As the efficacy of ART improves and PWH live longer, cardiovascular disease is increasing in prevalence in PWH [ 90 ]. PWH have a 2-fold increased prevalence of clonal hematopoiesis of indeterminate potential, the expansion of clonal hematopoietic stem cells due to leukemogenic mutations, which is associated with increased risks of coronary artery disease [ 91 , 92 ]. PWH have significantly increased rates of myocardial infarction (risk ratio, 1.79 [95% confidence interval {CI}, 1.54–2.08]) and stroke (risk ratio, 2.56 [95% CI, 1.43–4.61]) and a 2- to 10-fold increased risk of VTE, which is associated with increased D-dimer levels [ 93 ].…”

Section: Coagulation Disordersmentioning

confidence: 99%

Hematological Complications of Human Immunodeficiency Virus (HIV) Infection: An Update From an HIV-Endemic Setting

Opie,

Verburgh,

Bailly

et al. 2024

Open Forum Infectious Diseases

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Medical professionals, particularly in regions with a high burden of human immunodeficiency virus (HIV), should be alert to the hematological complications of HIV which may include cytopenias, malignancy and coagulation disturbances. Patients may present with these conditions as the first manifestation of HIV infection. Hematological abnormalities are often multifactorial with opportunistic infection, drugs, malignancy, and HIV infection itself contributing to the clinical presentation, and the diagnosis should consider all these factors. Life-threatening hematological complications requiring urgent diagnosis and management include thrombotic thrombocytopenic purpura, superior mediastinal syndrome, spinal cord compression and tumour lysis syndrome due to aggressive lymphoma. Antiretroviral therapy is the therapeutic backbone, including for patients with advanced disease, in addition to specific therapy for the complication. This article reviews the impact of HIV on the hematological system and provides a clinical and diagnostic approach, including the role of a bone marrow biopsy, focusing on perspectives from sub-Saharan Africa.

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“… 5 The excess risk is at least partly believed to be related to HIV’s activation of the immune system with resultant increased levels of proinflammatory proatherogenic cytokines, such as interleukin-6 (IL-6). 6 , 7 …”

Section: Introductionmentioning

confidence: 99%

Risk factors for clonal hematopoiesis of indeterminate potential in people with HIV: a report from the REPRIEVE trial

Bhattacharya,

Uddin,

Patel

et al. 2024

Blood Advances

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Clonal hematopoiesis of Indeterminate Potential (CHIP), the clonal expansion of myeloid cells with leukemogenic mutations, results in increased coronary artery disease (CAD) risk. CHIP is more prevalent among people with HIV (PWH) but the risk factors are unknown. CHIP was identified among PWH in REPRIEVE (Randomized Trial to Prevent Vascular Events in HIV) using whole exome sequencing (WES). Logistic regression was used to associate sociodemographic factors and HIV-specific factors with CHIP adjusting for age, sex, and smoking status. In the studied global cohort of 4,486 PWH, mean (SD) age was 49.9 (6.4) years, 1650 (36.8%) were female, and 3418 (76.2%) were non-White. CHIP was identified in 223/4486 (4.97%), and in 38/373 (10.2%) among those 60 years of age or older. Age (OR 1.07, 95%CI 1.05-1.09, p<0.0001) and smoking (OR 1.37, 95%CI 1.14-1.66, p<0.001) associated with increased odds of CHIP. Globally, participants outside of North America had lower odds of CHIP including Sub-Saharan Africa (OR 0.57, 95%CI 0.4-0.81, p=0.0019), South Asia (OR 0.45, 95%CI 0.23-0.80, p=0.01), and Latin America/Caribbean (OR 0.56, 95%CI 0.34-0.87, p=0.014). Hispanic/Latino ethnicity (OR 0.38, 95%CI 0.23-0.54, p=0.002) associated with significantly lower odds of CHIP. Among HIV-specific factors, CD4 nadir <50 cells/mm3 associated with a 1.9-fold (95%CI 1.21-3.05, p=0.006) increased odds of CHIP, with the effect being significantly stronger among individuals with short duration of antiretroviral therapy (ART) (OR 4.15, 95%CI 1.51-11.1, p=0.005) (pinteraction=0.0492). Among PWH at low-to-moderate CAD risk on stable ART, smoking, CD4 nadir, North American origin, and non-Hispanic ethnicity associated with increased odds of CHIP. Clinical Trials Registration: NCT02344290-

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Effect of Clonal Hematopoiesis on Cardiovascular Disease in People Living with HIV

Cited by 9 publications

References 17 publications

Clonal hematopoiesis of indeterminate potential in persons with HIV

Clonal hematopoiesis of indeterminate potential in persons with HIV

Hematological Complications of Human Immunodeficiency Virus (HIV) Infection: An Update From an HIV-Endemic Setting

Risk factors for clonal hematopoiesis of indeterminate potential in people with HIV: a report from the REPRIEVE trial

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