Impact of Early Antiretroviral Therapy Initiation on HIV-Specific CD4 and CD8 T Cell Function in Perinatally Infected Children
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE138804 | GEO | 2019/11/13
REPOSITORIES: GEO
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2021-02-17 | GSE158208 | 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. 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: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
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: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
Project description:HIV-Associated Neurocognitive Disorders (HAND) affect over half of HIV-infected individuals, despite antiretroviral therapy (ART). Therapeutically targetable mechanisms underlying HAND remain elusive, partly due to a lack of a proper model. We developed a human-induced pluripotent stem cell (HiPSC) based model, independently differentiating HiPSCs into neurons, astrocytes, and microglia, and systematically combining to generate a tri-culture with or without HIV-infection and ART. Single cell RNAseq analysis on tri-cultures with HIV-infected microglia revealed inflammatory signatures in the microglia and EIF2 signaling in all three cell types. Treatment with the antiretroviral compound EFZ mostly resolved these signatures. However, EFZ increased RhoGDI and CD40 signaling in the HIV-infected microglia. This activation was associated with a persistent increase in TNFa production by microglia. This work establishes a tri-culture that recapitulates key features of HIV infection in the CNS and provides a new model to examine the effects of infection, its treatment, and other co-morbid conditions.
2020-04-27 | GSE143686 | GEO
Project description:HIV-Associated Neurocognitive Disorders (HAND) affect over half of HIV-infected individuals, despite antiretroviral therapy (ART). Therapeutically targetable mechanisms underlying HAND remain elusive, partly due to a lack of a proper model. We developed a human-induced pluripotent stem cell (HiPSC) based model, independently differentiating HiPSCs into neurons, astrocytes, and microglia, and systematically combining to generate a tri-culture with or without HIV-infection and ART. Single cell RNAseq analysis on tri-cultures with HIV-infected microglia revealed inflammatory signatures in the microglia and EIF2 signaling in all three cell types. Treatment with the antiretroviral compound EFZ mostly resolved these signatures. However, EFZ increased RhoGDI and CD40 signaling in the HIV-infected microglia. This activation was associated with a persistent increase in TNFa production by microglia. This work establishes a tri-culture that recapitulates key features of HIV infection in the CNS and provides a new model to examine the effects of infection, its treatment, and other co-morbid conditions.
2020-04-27 | GSE143685 | GEO
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:Despite a successful antiretroviral therapy (ART), adolescents living with perinatally acquired HIV (PHIV) experience signs of B-cell hyperactivation with expansion of 'namely' atypical B-cell phenotypes, including double negative (CD27-IgD-) and termed age associated (ABCs) B-cells(T-bet+CD11c+), which may result in reduced cell functionality, including loss of vaccine-induced immunological memory and higher risk of developing B-cells associated tumors. In this context,perinatally HIV infected children (PHIV) deserve particular attention, given their life-long exposure to chronic immune activation.
2022-03-03 | PXD031908 | Pride
Project description:Introduction: HIV infection causes pathologic changes in the natural killer (NK) cell compartment that can be only partially restored by antiretroviral therapy (ART). We investigated NK cells phenotype and function in children with perinatally acquired HIV (PHIV) and long term viral control (5years) due to effective ART in a multicentre cross-sectional study (CARMA, EPIICAL consortium). The impact of age at ART start and viral reservoir was also evaluated. Methods: Peripheral Blood Mononuclear Cells (PBMCs) from 40 PHIV that started ART within two years of life (early treated patients, ET ≤ 6 months; late treated patients, LT > 6 months), with at least five years of HIV-1 suppression (< 40 HIV copies/ml), were collected between November 2017 and August 2018. NK phenotype and function were analysed by flow cytometry and transcriptional profile of PBMCs by RNA-Seq. HIV-1 DNA was measured by real-time PCR. Data were analysed by Spearman correlation plots and multivariable Poisson regression model (adjusted for baseline %CD4 and RNA HIV viral load and for age at ART start as interaction term, either ET or LT) to explore the association between NK cell parameters and HIV reservoir modulated by age at ART start. Results: A significantly higher frequency of CD56neg NK cells was found in LT compared with ET. We further found in LT a positive correlation of CD56neg NK with HIV-1 DNA. LT also displayed increased expression of the NKG2D and NKp46 activating receptors and perforin compared with ET. Moreover, CD107a+ and IFN-γ+ frequencies in non-stimulated NK were associated with HIV-1 DNA in LT patients. Finally, RNA-Seq analysis showed in LT an upregulation of genes related to NK activating pathways and susceptibility to apoptosis compared with ET. Conclusions: We show that ET present a preserved NK compartment compared with LT, which is associated with lower HIV-1 reservoir and persist despite long-term viral control due to effective ART.
2021-07-14 | GSE168658 | GEO