scholarly journals Increased CHIP Prevalence Amongst People Living with HIV

2020 ◽  
Author(s):  
Alexander G. Bick ◽  
Konstantin Popadin ◽  
Christian W. Thorball ◽  
Md Mesbah Uddin ◽  
Markella Zanni ◽  
...  
Keyword(s):  
Hematologic Malignancy ◽  
Driver Mutations ◽  
People Living With Hiv ◽  
Hematopoietic Stem ◽  
Age Related ◽  
Increased Risk ◽  
Propensity Matching ◽  
Study Population ◽  
Artery Disease ◽  
Living With Hiv

AbstractPeople 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.

scholarly journals Increased prevalence of clonal hematopoiesis of indeterminate potential amongst people living with HIV

2022 ◽  
Vol 12 (1) ◽  
Author(s):  
Alexander G. Bick ◽  
Konstantin Popadin ◽  
Christian W. Thorball ◽  
Md Mesbah Uddin ◽  
Markella V. Zanni ◽  
...  
Keyword(s):  
Hematologic Malignancy ◽  
Driver Mutations ◽  
People Living With Hiv ◽  
Hematopoietic Stem ◽  
Clonal Hematopoiesis ◽  
Age Related ◽  
Increased Risk ◽  
Study Population ◽  
Artery Disease ◽  
Living With Hiv

AbstractPeople 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 = 8111) from blood DNA-derived exome sequences. We observed that HIV is associated with a twofold increase in 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). We also observed that ASXL1 is the most commonly mutated CHIP-associated gene in PLWH. Our results suggest that CHIP may contribute to the excess cardiovascular risk observed in PLWH.

scholarly journals Inflammation and microbial translocation measured prior to combination antiretroviral therapy (cART) and long-term probability of clinical progression in people living with HIV

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Esther Merlini ◽  
Alessandro Cozzi-lepri ◽  
Antonella Castagna ◽  
Andrea Costantini ◽  
Sergio Lo Caputo ◽  
...  
Keyword(s):  
Cox Regression ◽  
Microbial Translocation ◽  
Study Cohort ◽  
People Living With Hiv ◽  
Clinical Progression ◽  
Cart Initiation ◽  
Increased Risk ◽  
Study Population ◽  
Hs Crp ◽  
Living With Hiv

Abstract Background Despite the effectiveness of cART, people living with HIV still experience an increased risk of serious non-AIDS events, as compared to the HIV negative population. Whether pre-cART microbial translocation (MT) and systemic inflammation might predict morbidity/mortality during suppressive cART, independently of other known risk factors, is still unclear. Thus, we aimed to investigate the role of pre-cART inflammation and MT as predictors of clinical progression in HIV+ patients enrolled in the Icona Foundation Study Cohort. Methods We included Icona patients with ≥2 vials of plasma stored within 6 months before cART initiation and at least one CD4 count after therapy available. Circulating biomarker: LPS, sCD14, EndoCab, hs-CRP. Kaplan-Meier curves and Cox regression models were used. We defined the endpoint of clinical progression as the occurrence of a new AIDS-defining condition, severe non-AIDS condition (SNAEs) or death whichever occurred first. Follow-up accrued from the data of starting cART and was censored at the time of last available clinical visit. Biomarkers were evaluated as both binary (above/below median) and continuous variables (logescale). Results We studied 486 patients with 125 clinical events: 39 (31%) AIDS, 66 (53%) SNAEs and 20 (16%) deaths. Among the analyzed MT and pro-inflammatory markers, hs-CRP seemed to be the only biomarker retaining some association with the endpoint of clinical progression (i.e. AIDS/SNAEs/death) after adjustment for confounders, both when the study population was stratified according to the median of the distribution (1.51 mg/L) and when the study population was stratified according to the 33% percentiles of the distribution (low 0.0–1.1 mg/L; intermediate 1.2–5.3 mg/L; high > 5.3 mg/L). In particular, the higher the hs-CRP values, the higher the risk of clinical progression (p = 0.056 for median-based model; p = 0.002 for 33% percentile-based model). Conclusions Our data carries evidence for an association between the risk of disease progression after cART initiation and circulating pre-cART hs-CRP levels but not with levels of MT. These results suggest that pre-therapy HIV-driven pro-inflammatory milieu might overweight MT and its downstream immune-activation.

scholarly journals Interacting evolutionary pressures drive mutation dynamics and health outcomes in aging blood

2020 ◽  
Author(s):  
Kimberly Skead ◽  
Armande Ang Houle ◽  
Sagi Abelson ◽  
Mawusse Agbessi ◽  
Vanessa Bruat ◽  
...  
Keyword(s):  
Negative Selection ◽  
Sequence Data ◽  
Relative Proportion ◽  
Selective Advantage ◽  
Driver Mutations ◽  
Driver Genes ◽  
Hematopoietic Stem ◽  
Age Related ◽  
Increased Risk ◽  
Passenger Mutations

AbstractA small population of self-renewing, hematopoietic stem cells continuously reconstitutes our immune system. As we age, these cells, or their pluripotent descendants, accumulate somatic mutations; some of these mutations provide selection advantages and increase in frequency in the peripheral blood cell population. This process of positive selection, deemed age-related clonal hematopoiesis (ARCH), is associated with increased risk for cardiac disease and blood malignancies, like acute myeloid leukemia (AML). However, it remains unclear why some people with ARCH do not progress to AML, even when their blood cells harbor well-known AML driver mutations. Here, we examine whether negative selection can play a role in determining AML progression by modelling the complex interplay of positive and negative selective processes. Using a novel approach combining deep learning and population genetic models, we detect pervasive negative selection in targeted sequence data from the blood of 92 pre-AML individuals and 385 healthy controls. We find that the relative proportion of passenger to driver mutations is critical in determining if the selective advantage conferred to a cell by a known driver mutation is able to overwhelm negative selection acting on passenger mutations and allow clones harbouring disease-predisposing mutations to rise to dominance. We find that a subset of non-driver genes is enriched for mildly damaging mutations in healthy individuals fitting purifying models of evolution suggesting that mutations in these genes might confer a protective role against disease-predisposing clonal expansions. Through exploring non drivercentric models of evolution, we show how different classes of evolution act to shape hematopoietic dynamics and subsequent health outcome which may better inform disease prediction and unveil novel therapeutic targets. We anticipate that our results and modelling techniques can be broadly applied to identify both driver mutations and those mildly damaging passenger mutations, as well as help understand the early evolution of cancer in other cells and tissues.

scholarly journals Altered Lipid Profiles and Vaccine Induced-Humoral Responses in Children Living With HIV on Antiretroviral Therapy in Tanzania

2021 ◽  
Vol 11 ◽  
Author(s):  
Wilbert Mbuya ◽  
Issakwisa Mwakyula ◽  
Willyelimina Olomi ◽  
Peter Agrea ◽  
Francesco Nicoli ◽  
...  
Keyword(s):  
Antiretroviral Therapy ◽  
Pertussis Toxin ◽  
Density Lipoprotein ◽  
Lipid Profiles ◽  
Antibody Responses ◽  
People Living With Hiv ◽  
Age Related ◽  
Fold Reduction ◽  
Increased Risk ◽  
Living With Hiv

People living with HIV, even under therapy, have a high burden of age-related co-morbidities including an increased risk of dyslipidemia (which often predisposes to cardiovascular diseases) and immune-aging. In this study, lipid profiles and antibody responses to measles and pertussis toxin vaccines were compared between ART experienced HIV+ children (n=64) aged 5-10 years, and their age- and sex-matched HIV- controls (n=47). Prevalence of high-density lipoprotein cholesterol (HDL-c) and triglyceride-driven dyslipidemia was higher among treated HIV+ children than in controls (51.6% vs 27.7% respectively, p < 0.019). In a multivariate Poisson regression model adjusted for age, sex and BMI, the association between low HDL-c, hypertriglyceridemia and HIV remained significantly high (for HDL-c: ARR: 0.89, 95% CI: 0.82 – 0.96, p = 0.003; for triglycerides: ARR: 1.54, 95% CI: 1.31 – 1.81, p < 0.001). Among HIV+ children, the use of lopinavir/ritonavir, a protease-based antiretroviral therapy was also associated elevation of triglyceride levels (p = 0.032). Also, HIV+ children had a 2.8-fold reduction of anti-measles IgG titers and 17.1-fold reduction of anti-pertussis toxin IgG levels when compared to HIV- children. Our findings suggest that dyslipidemia and inadequate vaccine-induced antibody responses observed in this population of young African HIV+ children might increase their risk for premature onset of cardiovascular illnesses and acquisition of preventable diseases.

Living with HIV in the Time of COVID-19

2020 ◽  
Vol 10 (1) ◽  
pp. 5-7
Author(s):  
Muhammad Naveed Noor
Keyword(s):  
Medical Care ◽  
Developing Country ◽  
People Living With Hiv ◽  
Evidence Based ◽  
Comorbid Conditions ◽  
Increased Risk ◽  
Associated Conditions ◽  
Living With Hiv

This commentary foregrounds the need to examine how the coronavirus disease 2019 (COVID-19) pandemic and associated conditions may be affecting the lives of people living with HIV (PLWH) in a developing country context like Pakistan. It raises some important questions on medical care and updated information regarding PLWH in the time of COVID-19. Since PLWH are at an increased risk of developing comorbid conditions – something that makes them more vulnerable to COVID-19 – it is critical that timely research and evidence-based actions are undertaken to protect their health.

Prevalence of Asymptomatic Cryptococcal Antigenemia and Association with Follow-up risk of Cryptococcal Meningitis and Mortality among HIV Infected Patients in North West India – A Prospective Cohort Study

2020 ◽  
Vol 18 ◽  
Author(s):  
Rajendra Bhati ◽  
Pramendra Sirohi ◽  
Bharat Sejoo ◽  
Deepak Kumar ◽  
Gopal K Bohra ◽  
...  
Keyword(s):  
Cryptococcal Meningitis ◽  
Morbidity And Mortality ◽  
People Living With Hiv ◽  
Cryptococcal Antigen ◽  
North West ◽  
Cryptococcal Disease ◽  
Increased Risk ◽  
Living With Hiv ◽  
Inflammatory Syndrome

Objective: Cryptococcal meningitis is an important cause of morbidity and mortality in HIV infected individuals. In the era of universal antiretroviral therapy incidence of immune reconstitution inflammatory syndrome (IRIS) related cryptococcal meningitis has increased. Detection of serum cryptococcal antigen in asymptomatic PLHIV (People Living With HIV) and pre-emptive treatment with fluconazole can decrease the burden of cryptococcal disease. We conducted this study to find the prevalence of asymptomatic cryptococcal antigenemia in India and its correlation with mortality in PLHIV. Method and material: This was a prospective observational study. HIV infected ART naïve patients with age of ≥ 18 years who had CD4 counts ≤ 100 /µL were included and serum cryptococcal antigen test was done. These patients were followed for six months to look for the development of Cryptococcal meningitis and mortality. Results: A total of 116 patients were analysed. Asymptomatic cryptococcal antigenemia was detected in 5.17% patients and it correlated with increased risk of cryptococcal meningitis and mortality on follow-up in PLHIV. Conclusion: Serum cryptococcal positivity is correlated with increased risk of Cryptococcal meningitis and mortality in PLHIV. We recommend the screening of asymptomatic PLHIV with CD4 ≤ 100/µL for serum cryptococcal antigen, so that pre-emptive treatment can be initiated to reduce morbidity and mortality.

scholarly journals Stigma mastery in people living with HIV: gender similarities and theory

2021 ◽  
Author(s):  
Charles Patrick Namisi ◽  
John C. Munene ◽  
Rhoda K. Wanyenze ◽  
Anne R. Katahoire ◽  
Rosalinda M. Parkes-Ratanshi ◽  
...  
Keyword(s):  
Older Women ◽  
Social Exclusion ◽  
Theoretical Framework ◽  
People Living With Hiv ◽  
Negative Effects ◽  
Hiv Diagnosis ◽  
Cross Sectional ◽  
Age Related ◽  
Related Stigma ◽  
Living With Hiv

Abstract Aims This study aimed to determine the prevalence of, factors associated with, and to build a theoretical framework for understanding Internalsed HIV-related Stigma Mastery (IHSM). Methods A cross-sectional study nested within a 2014 Stigma Reduction Cohort in Uganda was used. The PLHIV Stigma Index version 2008, was used to collect data from a random sample of 666 people living with HIV (PLHIV) stratified by gender and age. SPSS24 with Amos27 softwares were used to build a sequential-mediation model. Results The majority of participants were women (65%), aged ≥ 40 years (57%). Overall, IHSM was 45.5% among PLHIV, that increased with age. Specifically, higher IHSM correlated with men and older women “masculine identities” self-disclosure of HIV-diagnosis to family, sharing experiences with peers. However, lower IHSM correlated with feminine gender, the experience of social exclusion stress, fear of future rejection, and fear of social intimacy. Thus, IHSM social exclusion with its negative effects and age-related cognition are integrated into a multidimensional IHSM theoretical framework with a good model-to-data fit. Conclusion Internalised HIV-related Stigma Mastery is common among men and older women. Specificially, “masculine identities” self-disclose their own HIV-positive diagnosis to their family, share experiences with peers to create good relationships for actualising or empowerment in stigma mastery. However, social exclusion exacerbates series of negative effects that finally undermine stigma mastery by young feminine identities. Thus, stigma mastery is best explained by an integrated empowerment framework, that has implications for future practice, policy, and stigma-related research that we discuss.

scholarly journals An Emerging Syndemic of Smoking and Cardiopulmonary Diseases in People Living with HIV in Africa

2021 ◽  
Vol 18 (6) ◽  
pp. 3111
Author(s):  
Emmanuel Peprah ◽  
Mari Armstrong-Hough ◽  
Stephanie H. Cook ◽  
Barbara Mukasa ◽  
Jacquelyn Y. Taylor ◽  
...  
Keyword(s):  
Current Evidence ◽  
Chronic Obstructive ◽  
People Living With Hiv ◽  
African Countries ◽  
Obstructive Pulmonary Disease ◽  
Cardiopulmonary Disease ◽  
Current Trends ◽  
Significant Public Health ◽  
Artery Disease ◽  
Living With Hiv

Background: African countries have the highest number of people living with HIV (PWH). The continent is home to 12% of the global population, but accounts for 71% of PWH globally. Antiretroviral therapy has played an important role in the reduction of the morbidity and mortality rates for HIV, which necessitates increased surveillance of the threats from pernicious risks to which PWH who live longer remain exposed. This includes cardiopulmonary comorbidities, which pose significant public health and economic challenges. A significant contributor to the cardiopulmonary comorbidities is tobacco smoking. Indeed, globally, PWH have a 2–4-fold higher utilization of tobacco compared to the general population, leading to endothelial dysfunction and atherogenesis that result in cardiopulmonary diseases, such as chronic obstructive pulmonary disease and coronary artery disease. In the context of PWH, we discuss (1) the current trends in cigarette smoking and (2) the lack of geographically relevant data on the cardiopulmonary conditions associated with smoking; we then review (3) the current evidence on chronic inflammation induced by smoking and the potential pathways for cardiopulmonary disease and (4) the multifactorial nature of the syndemic of smoking, HIV, and cardiopulmonary diseases. This commentary calls for a major, multi-setting cohort study using a syndemics framework to assess cardiopulmonary disease outcomes among PWH who smoke. Conclusion: We call for a parallel program of implementation research to promote the adoption of evidence-based interventions, which could improve health outcomes for PWH with cardiopulmonary diseases and address the health inequities experienced by PWH in African countries.

scholarly journals DNA methylation is associated with airflow obstruction in patients living with HIV

Thorax ◽  
2020 ◽  
pp. thoraxjnl-2020-215866
Author(s):  
Ana I Hernandez Cordero ◽  
Chen Xi Yang ◽  
Maen Obeidat ◽  
Julia Yang ◽  
Julie MacIsaac ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Lung Function ◽  
Viral Infections ◽  
Airflow Obstruction ◽  
Normal Lung ◽  
People Living With Hiv ◽  
Global Methylation ◽  
Age Related ◽  
Impaired Lung Function ◽  
Living With Hiv

IntroductionPeople living with HIV (PLWH) suffer from age-related comorbidities such as COPD. The processes responsible for reduced lung function in PLWH are largely unknown. We performed an epigenome-wide association study to investigate whether blood DNA methylation is associated with impaired lung function in PLWH.MethodsUsing blood DNA methylation profiles from 161 PLWH, we tested the effect of methylation on FEV1, FEV1/FVC ratio and FEV1 decline over a median of 5 years. We evaluated the global methylation of PLWH with airflow obstruction by testing the differential methylation of transposable elements Alu and LINE-1, a well-described marker of epigenetic ageing.ResultsAirflow obstruction as defined by a FEV1/FVC<0.70 was associated with 1393 differentially methylated positions (DMPs), while 4676 were associated with airflow obstruction based on the FEV1/FVC<lower limit of normal. These DMPs were enriched for biological pathways associated with chronic viral infections. The airflow obstruction group was globally hypomethylated compared with those without airflow obstruction. 103 and 7112 DMPs were associated with FEV1 and FEV1/FVC, respectively. No positions were associated with FEV1 decline.ConclusionA large number of DMPs were associated with airflow obstruction and lung function in a unique cohort of PLWH. Airflow obstruction in even relatively young PLWH is associated with global hypomethylation, suggesting advanced epigenetic ageing compared with those with normal lung function. The disturbance of the epigenetic regulation of key genes not previously identified in non-HIV COPD cohorts could explain the unique risk of COPD in PLWH.

scholarly journals The Genetics of Myelodysplastic Syndromes: Clinical Relevance

Genes ◽  
2021 ◽  
Vol 12 (8) ◽  
pp. 1144
Author(s):  
Chiara Chiereghin ◽  
Erica Travaglino ◽  
Matteo Zampini ◽  
Elena Saba ◽  
Claudia Saitta ◽  
...  
Keyword(s):  
Disease Progression ◽  
Myelodysplastic Syndromes ◽  
Clinical Relevance ◽  
Driver Mutations ◽  
Significant Information ◽  
Hematopoietic Stem ◽  
Probability Of Survival ◽  
Mutational Status ◽  
Increased Risk ◽  
Risk Of Disease

Myelodysplastic syndromes (MDS) are a clonal disease arising from hematopoietic stem cells, that are characterized by ineffective hematopoiesis (leading to peripheral blood cytopenia) and by an increased risk of evolution into acute myeloid leukemia. MDS are driven by a complex combination of genetic mutations that results in heterogeneous clinical phenotype and outcome. Genetic studies have enabled the identification of a set of recurrently mutated genes which are central to the pathogenesis of MDS and can be organized into a limited number of cellular pathways, including RNA splicing (SF3B1, SRSF2, ZRSR2, U2AF1 genes), DNA methylation (TET2, DNMT3A, IDH1/2), transcription regulation (RUNX1), signal transduction (CBL, RAS), DNA repair (TP53), chromatin modification (ASXL1, EZH2), and cohesin complex (STAG2). Few genes are consistently mutated in >10% of patients, whereas a long tail of 40–50 genes are mutated in <5% of cases. At diagnosis, the majority of MDS patients have 2–4 driver mutations and hundreds of background mutations. Reliable genotype/phenotype relationships were described in MDS: SF3B1 mutations are associated with the presence of ring sideroblasts and more recent studies indicate that other splicing mutations (SRSF2, U2AF1) may identify distinct disease categories with specific hematological features. Moreover, gene mutations have been shown to influence the probability of survival and risk of disease progression and mutational status may add significant information to currently available prognostic tools. For instance, SF3B1 mutations are predictors of favourable prognosis, while driver mutations of other genes (such as ASXL1, SRSF2, RUNX1, TP53) are associated with a reduced probability of survival and increased risk of disease progression. In this article, we review the most recent advances in our understanding of the genetic basis of myelodysplastic syndromes and discuss its clinical relevance.

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