Effect of HIV infection and antiretroviral therapy initiation on genome-wide DNA methylation patterns.
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ABSTRACT:
PROVIDER: PRJNA899859 | ENA |
REPOSITORIES: ENA
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Project description:Background. Previous epigenome-wide association studies have shown that HIV infection can disrupt the host DNA methylation landscape. However, it remains unclear how antiretroviral therapy (ART) affects the HIV-induced epigenetic modifications. Methods. 184 individuals with HIV from the NEAT001/ANRS143 clinical trial (with pre-ART and post-ART samples [96 weeks of follow-up]) and 44 age-and-sex matched individuals without HIV were included. We compared genome-wide DNA methylation profiles in whole blood between groups adjusting for age, sex, batch effects, and leucocyte type heterogeneity. Findings. We identified 430 differentially methylated positions (DMPs) between HIV+ pre-ART individuals and HIV-uninfected controls. In participants with HIV, ART initiation modified the DNA methylation levels at 845 CpG positions and restored 49.3% of the changes found between HIV+ pre-ART and HIV-uninfected individuals. We only found 15 DMPs when comparing DNA methylation profiles between HIV+ post-ART individuals and participants without HIV. The Gene Ontology enrichment analysis of DMPs associated with untreated HIV infection revealed an enrichment in biological processes regulating the immune system and antiviral responses. In participants with untreated HIV infection, DNA methylation levels at top HIV-related DMPs were associated with CD4/CD8 ratios and viral loads. Changes in DNA methylation levels after ART initiation were weakly correlated with changes in CD4+ cell counts and the CD4/CD8 ratio. Interpretation. Control of HIV viraemia after 96 weeks of ART initiation restores most of the host DNA methylation changes that occurred before antiretroviral treatment of HIV infection.
2023-01-16 | GSE217633 | GEO
Project description:Tuberculosis-associated Immune Reconstitution Inflammatory Syndrome (TB-IRIS) is a common complication in HIV-TB co-infected patients receiving combined antiretroviral therapy (cART). While monocytes/macrophages play major roles in both HIV- and TB-infection individually, a putative contribution of monocytes to the development of TB-IRIS remains unexamined. We performed a genome-wide array analysis on MOs purified from peripheral blood mononuclear cells (PBMCs) obtained before initiation of combined antiretroviral therapy (cART) to verify whether the transcriptome of MOs was already significantly modulated (even before receiving cART) in HIV+/TB+ patients who later developed TB-IRIS compared to control HIV+/TB+ patients who did not develop the complication . The subjects under study included a subset of 18 TB-IRIS patients and controls matched for age, gender and CD4 count.
2013-04-01 | E-MEXP-3618 | biostudies-arrayexpress
Project description:We aim to characterize HIV and HCV coinfected patient response to combined antiretroviral therapy through genome-wide expression profiling of patients' periperhal blood mononuclear cells before and after treatment initiation (baseline and 24 weeks). Individuals with frank cirrhosis were excluded from the study. We used Affymetrix PrimeView arrays to quantify baseline transcriptomic characteristics and changes in the transcriptome following treatment. Gene expression changes were analyzed based on the change in expression of each transcript per patient. Mononuclear cells were purified from peripheral blood samples of 8 patients with HIV and HCV coinfection at baseline and after 24 weeks of combined antiretroviral therapy. Genes from whole blood RNA was measured via Affymetrix PrimeView microarrays.
2014-10-07 | E-GEOD-56619 | biostudies-arrayexpress
Project description:Exploratory microarray analysis identified significant changes in gene expression in adipose tissue. These included changes in genes regulating lipid and steroid metabolic processes and electron carrier activity in HIV-infected patients receiving antiretroviral therapy (ART). Additional genes involved in metabolic processes and mitochondrial function were found to be up-regulated in the adipose tissue of HIV-positive patients compared with HIV-negative controls. To identify differential gene expression in different tissues (PBMC, muscle, adipose tissue) between HIV patient groups (HIV negative, HIV positive with ART, HIV positive without ART).
2011-07-07 | E-GEOD-30310 | biostudies-arrayexpress
Project description:A growing body of data suggests that the human brain serves as a sanctuary for HIV persistence despite life-long antiretroviral therapy. Microglia, the innate immune cells of the brain parenchyma, may serve as a reservoir for rebound of HIV infection. The extent of the latent brain reservoir and molecular phenotype of HIV infected microglia cells, however, are unknown. To address this major knowledge gap, we leveraged the ‘Last Gift’ rapid autopsy cohort to perform a multi-omics approach (single cell RNA-seq, single cell ATAC-seq, and H3K27ac ChIP-seq) of the myeloid compartment creating a gene expression and chromatin accessibility atlas of human microglia isolated from three male individuals with HIV on suppressive antiretroviral therapy.
2024-02-01 | GSE221686 | GEO
Project description:A growing body of data suggests that the human brain serves as a sanctuary for HIV persistence despite life-long antiretroviral therapy. Microglia, the innate immune cells of the brain parenchyma, may serve as a reservoir for rebound of HIV infection. The extent of the latent brain reservoir and molecular phenotype of HIV infected microglia cells, however, are unknown. To address this major knowledge gap, we leveraged the ‘Last Gift’ rapid autopsy cohort to perform a multi-omics approach (single cell RNA-seq, single cell ATAC-seq, and H3K27ac ChIP-seq) of the myeloid compartment creating a gene expression and chromatin accessibility atlas of human microglia isolated from three male individuals with HIV on suppressive antiretroviral therapy.
2024-02-01 | GSE221685 | GEO
Project description:A growing body of data suggests that the human brain serves as a sanctuary for HIV persistence despite life-long antiretroviral therapy. Microglia, the innate immune cells of the brain parenchyma, may serve as a reservoir for rebound of HIV infection. The extent of the latent brain reservoir and molecular phenotype of HIV infected microglia cells, however, are unknown. To address this major knowledge gap, we leveraged the ‘Last Gift’ rapid autopsy cohort to perform a multi-omics approach (single cell RNA-seq, single cell ATAC-seq, and H3K27ac ChIP-seq) of the myeloid compartment creating a gene expression and chromatin accessibility atlas of human microglia isolated from three male individuals with HIV on suppressive antiretroviral therapy.
2024-02-01 | GSE221687 | GEO
Project description:We compared transcriptional profiles of CD4+ and CD8+ T lymphocytes from HIV infected individuals before and 1 year after interruption of antiretroviral therapy (ART).
2018-01-01 | GSE98902 | GEO
Project description:Initiation of antiretroviral therapy during the earliest stages of HIV-1 infection may limit the seeding of a long-lasting viral reservoir, but long-term effects of early antiretroviral treatment initiation remain unknown. Here, we analyzed immunological and virological characteristics of nine patients who started antiretroviral therapy in primary HIV-1 infection and remained on suppressive treatment for >10 years; patients with similar treatment duration but initiation of therapy in chronic HIV-1 infection served as controls. We observed that independently of the timing of treatment initiation, HIV-1 DNA in CD4 T cells decayed exclusively during the initial 3-4 years of treatment; however, in patients who started antiretroviral therapy in acute infection, this decay occurred faster and was more pronounced, leading to substantially lower levels of cell-associated HIV-1 DNA after long-term treatment. Despite this smaller size, the viral CD4 T cell reservoir in persons with early treatment initiation consisted more dominantly of the long-lasting central-memory and T memory stem cells. Moreover, gene transcripts in CD4 T cells associated with the total viral CD4 T cell reservoir size frequently correlated with the relative proportion of these long-lived CD4 T cell subsets, suggesting shared gene expression signatures for maintaining HIV-1 persistence and preservation of long-lasting CD4 T cell subsets. Despite effective suppression of viral antigens for >10 years, HIV-1-specific T cell responses remained continuously detectable in both study groups. Together, these data suggest that although early HIV-1 treatment initiation, even when continued for >10 years, is unlikely to lead to viral eradication, the presence of low viral reservoirs and durable HIV-1 T cell responses may make such patients attractive candidates for future interventional studies aiming at HIV-1 eradication and cure.
2017-01-01 | GSE53527 | GEO
Project description:Exploratory microarray analysis identified significant changes in gene expression in adipose tissue. These included changes in genes regulating lipid and steroid metabolic processes and electron carrier activity in HIV-infected patients receiving antiretroviral therapy (ART). Additional genes involved in metabolic processes and mitochondrial function were found to be up-regulated in the adipose tissue of HIV-positive patients compared with HIV-negative controls.
2011-07-07 | GSE30310 | GEO