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Dominant CD4+ T cell receptors remain stable throughout antiretroviral therapymediated immune restoration in people with HIV

ABSTRACT: In people with HIV (PWH), the post antiretroviral therapy (ART) window is critical for immune restoration and HIV reservoir stabilization. We employ deep immune profiling, T cell receptor (TCR) sequencing and examine proliferation to assess how ART impacts T cell homeostasis. Hierarchies and frequencies of dominant CD4 TCR clonotypes (0.1-11% of all CD4+ T cells) remain stable post-ART, suggesting that clonal homeostasis can be independent of homeostatic processes regulating CD4+T cell absolute number, phenotypes and function. The slow restoration of host-immunity post-ART also has implications for the design of ART interruption studies.

ORGANISM(S): Homo sapiens

PROVIDER: GSE244867 | GEO | 2023/10/09

REPOSITORIES: GEO

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Effect of HIV infection and antiretroviral therapy initiation on genome-wide DNA methylation patterns.

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

Profiling of proteome changes in plasma of HIV-infected patients receiving antiretroviral therapy

Project description:Antiretroviral therapy (ART) prevents HIV-1 onward transmission and disease progression, leading to excellent prognosis people living with HIV-1 (PWH). However, significant side effects, complications and impaired immune reconstitution still persist along with ART. We aimed to profile proteome changes in plasma before and after ART to identify the molecular pathways altered by ART and finding potential targets to improve the health of PWH.

2022-03-08 | PXD045070 | iProX

Distinct Intestinal Microbial Signatures Linked to Accelerated Biological Aging in People with HIV

Project description:Genome-wide DNA methylation profiling of colon and ileal biopsies, blood samples from people living with HIV on ART and their matched HIV-negative counterparts. Despite having similar chronological ages, PWH on ART exhibit accelerated biological aging in the colon, ileum, and blood, as measured by various epigenetic aging clocks, compared to HIV-negative controls. Investigating the relationship between microbial translocation and biological aging, PWH on ART had decreased levels of tight junction proteins in the colon and ileum, along with increased microbial translocation.

2024-02-28 | GSE245924 | GEO

Impact of Early Antiretroviral Therapy Initiation on HIV-Specific CD4 and CD8 T Cell Function in Perinatally Infected Children

Project description:14 children vertically HIV infected ART treated within 6 months of life (ET) and 6 children vertically HIV infected ART treated after 12 months of life were studied to understand the effect of early ART initiation on HIV specific CD4+ T cells and CD8+ T cells functionalities. Additionally, RNAseq on unstimulated PBMC was performed to also evaluate the impact of early ART on the immune transcriptome.

2019-11-13 | GSE138804 | GEO

Single-cell TCR profiling of CSF and blood cells of PWH reveals persistent and shared infected T cell clones across tissue compartments even after ART

Project description:The brain is a site of persistent infected cells during HIV infection. However, the dynamics of central nervous system (CNS) infection and T cell trafficking in people living with HIV (PWH) are incompletely understood. We profiled the single cell T cell repertoire and host transcriptome from paired blood and cerebrospinal fluid (CSF) from PWH and uninfected controls. We detected HIV RNA-producing cells in 8/11 (72.7 %) CSF samples and 6/11 (54.5 %) blood samples, with a higher frequency of infected single CD4 T cells in CSF than in blood. Infected CSF T cells displayed a unique transcriptional profile compared to uninfected CSF T cells. Most infected T cell clones were not shared across tissue; however, in a subset of participants we detected identical T cell clones that were infected in both CSF and blood. Longitudinally following one PWH before and at three time points after initiating ART, we found infected T cell clones that persisted after ART initiation, in both CSF and blood, including a T cell clone that expanded in the CSF several months after ART initiation. Our findings suggest that infected T cells traffic to the CNS where they undergo clonal expansion despite ART, contributing to the CNS reservoir.

2024-04-15 | GSE243905 | GEO

Significant Effects of Antiretroviral Therapy on Global Gene Expression in Brain Tissues of Patients with HIV-Associated Neurocognitive Disorders

2011-09-25 | GSE28160 | GEO

Epigenetic Features of HIV-Induced T-Cell Exhaustion Persist Despite Early Antiretroviral Therapy

Project description:T cell dysfunction occurs early following HIV infection, impacting the emergence of non-AIDS morbidities and limiting curative efforts. ART initiated during primary HIV infection (PHI) can reverse this dysfunction, but the extent of recovery is unknown. We studied 66 HIV-infected individuals treated from early PHI with up to three years of ART. Compared with HIV-uninfected controls, CD4 and CD8 T cells from early HIV infection were characterised by T cell activation and increased expression of the immune checkpoint receptors (ICRs) PD1, Tim-3 and TIGIT. Three years of ART lead to partial – but not complete – normalisation of ICR expression, the dynamics of which varied for individual ICRs. For HIV-specific cells, epigenetic profiling of tetramer-sorted CD8 T cells revealed that epigenetic features of exhaustion typically seen in chronic HIV infection were already present early in PHI, and that ART initiation during PHI resulted in only a partial shift of the epigenome to one with more favourable memory characteristics. These findings suggest that although ART initiation during PHI results in significant immune reconstitution, there may be only partial resolution of HIV-related phenotypic and epigenetic changes.

2023-07-19 | GSE237729 | GEO

Effect of Analytic Treatment Interruption of Antiretroviral Therapy on HIV Reservoirs and Immunological Parameters

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

Significant Effects of Antiretroviral Therapy on Global Gene Expression in Brain Tissues of Patients with HIV-Associated Neurocognitive Disorders

Project description:Antiretroviral therapy (ART) has reduced morbidity and mortality in HIV infection; however HIV-1-associated neurocognitive disorders (HAND) persist despite treatment. We used microarray analysis in post-mortem brain tissues to determine ART effectiveness in the brain and to identify molecular signatures of HAND under ART. We performed microarray analysis using Affymetrix Arrays in portmortem brain tissues from seven treated and eight untreated HAND patients and six uninfected controls.

2011-09-24 | E-GEOD-28160 | biostudies-arrayexpress

HIV Infection and Antiretroviral Therapy Have Divergent Effects on Mitochondria in Adipose Tissue

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

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