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Expression data from HAART interruption in HIV patients

ABSTRACT: We evaluated longitudinal changes in viral replication and emergence of viral variants in the context of T cell homeostasis and gene expression in GALT of three HIV-positive patients who initiated HAART during primary HIV infection but opted to interrupt therapy thereafter. Longitudinal viral sequence analysis revealed that a stable proviral reservoir was established in GALT during primary HIV infection that persisted through early HAART and post-therapy interruption. Proviral variants in GALT and peripheral blood mononuclear cells (PBMCs) displayed low levels of genomic diversity at all times. A rapid increase in viral loads with a modest decline of CD4 T cells in peripheral blood was observed, while gut mucosal CD4 T cell loss was severe following HAART interruption. This was accompanied by increased mucosal gene expression regulating interferon (IFN)-mediated antiviral responses and immune activation, a profile similar to those found in HAART-naive HIV-infected patients.

ORGANISM(S): Homo sapiens

PROVIDER: GSE28177 | GEO | 2011/03/26

SECONDARY ACCESSION(S): PRJNA139527

REPOSITORIES: GEO

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Expression data from HAART interruption in HIV patients

Project description:We evaluated longitudinal changes in viral replication and emergence of viral variants in the context of T cell homeostasis and gene expression in GALT of three HIV-positive patients who initiated HAART during primary HIV infection but opted to interrupt therapy thereafter. Longitudinal viral sequence analysis revealed that a stable proviral reservoir was established in GALT during primary HIV infection that persisted through early HAART and post-therapy interruption. Proviral variants in GALT and peripheral blood mononuclear cells (PBMCs) displayed low levels of genomic diversity at all times. A rapid increase in viral loads with a modest decline of CD4 T cells in peripheral blood was observed, while gut mucosal CD4 T cell loss was severe following HAART interruption. This was accompanied by increased mucosal gene expression regulating interferon (IFN)-mediated antiviral responses and immune activation, a profile similar to those found in HAART-naive HIV-infected patients. Gut mucosal responses to HAART interruption were evaluated with Affymetrix arrays

2011-03-25 | E-GEOD-28177 | biostudies-arrayexpress

Homo sapiens

Project description:Expression data from HAART interruption in HIV patients

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

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DC immunotherapy in HIV-1 infection induces a major blood transcriptome shift

Project description:Objective: This study aimed to evaluate the effect of dendritic cell (DC) vaccination against HIV-1 on host gene expression profiles. Design: Longitudinal PBMC samples were collected from participants of the DC-TRN trial for immunotherapy against HIV. Microarray-assisted gene expression profiling was performed to evaluate the effects of vaccination and subsequent interruption of antiretroviral therapy on host genome expression. Data from the DC-TRN trial were compared with results from other vaccination trials. Methods: We used Affymetrix GeneChips for microarray gene expression analysis. Data were analyzed by principal component analysis and differential gene expression was assessed using linear modeling. Gene ontology enrichment and gene set analysis were used to characterize differentially expressed genes. Transcriptome analysis included comparison with PBMCs obtained from DC-vaccinated melanoma patients and of healthy individuals who received seasonal influenza vaccination. Results: DC-TRN immunotherapy in HIV-infected individuals resulted in a major shift in the transcriptome. Longitudinal analysis demonstrated that changes in the transcriptome sustained also during interruption of antiretroviral therapy. After DC-vaccination, the transcriptome was enriched for cellular immunity associated genes that were also induced in healthy adults who received live attenuated influenza virus vaccination. These beneficial responses were accompanied by detrimental signals of general immune activation. Conclusions: The DC-TRN induced changes in the transcriptome were profound, lasting, and consisted of both protective signals and signatures of inflammation and immune exhaustion, with a net result of decreased viral load, without clinical benefit. Thus transcriptome analysis provides useful information, dissecting both positive and negative effects, for the evaluation of safety and efficacy of immunotherapeutic strategies.

2015-04-30 | E-MTAB-3296 | biostudies-arrayexpress

Longitudinal comparison of monocytes from an HIV viremic vs avirmeic state

Project description:Longitudinal analysis of monocyte gene expressions patterns before and after cessation of HAART: understanding the impact of HIV viremia on the monocyte tranascritome. We used microarrays to detail the global program of gene expression underlying defects in monocytes from HIV infected patients during viremia.. Diminished Production of Monocyte Proinflammatory Cytokines During HIV Viremia is Mediated by Interferon-alpha: The in vivo effect of high-level HIV replication on the function of monocytes was investigated. HIV-positive patients had elevated spontaneous production of monocyte proinflammatory cytokines (IL-1?, IL-6, and TNF-?) compared to uninfected controls. These levels were highest in patients on-therapy and was diminished, in the context of viremia, following an interruption of therapy. Diminished production of proinflammatory cytokines during viremia was restored by culturing with autologous CD4+ T cells or monocytes from an on-therapy time point, or by the addition of lipopolysaccharide (LPS). Microarray analysis demonstrated that diminished monocyte production of proinflammatory cytokines was correlated with elevated levels of type I interferon-stimulated gene transcripts. Addition of exogenous IFN-?2A suppressed the spontaneous production of IL-1?, IL-6, and TNF-? but did not affect responses to LPS, recapitulating the changes observed in HIV viremic patients. These results suggest that high-level HIV viremia inhibits monocyte function through chronic stimulation by IFN-?. This effect of viremia on monocytes may play a role in diminished adaptive immune system functions in HIV-infected patients. Restoration of these functions may contribute to the partial immune reconstitution observed following therapy and may be involved in immune reconstitution and inflammatory syndrome seen in some patients. Keywords: Longitudinal comparison

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Project description:Systemic and local (oral mucosal) immune responses in acutely infected HIV individuals before the initiation of HAART have not been well characterized. Protein microarrays were used to analyze saliva and plasma from HIV infected and HIV uninfected subjects to identify new biomarkers for HIV disease progression and pathogenesis. A 507 protein microarray was employed to provide a broad view of cytokines and chemokines in saliva and plasma in acutely HIV infected subjects as compared to uninfected subjects. A custom array derived from the initial results was refined to highlight those molecules with significant change relative to control subjects indicating the potential for biological impact.

2011-09-08 | E-GEOD-24037 | biostudies-arrayexpress

Salivary cytokine alterations in HIV infection part 2

Project description:A 507 protein microarray was employed to provide a broad view of cytokines and chemokines in saliva and plasma in acutely HIV infected subjects as compared to uninfected subjects. A 40 cytokine custom array derived from the initial results was refined to highlight those molecules with significant change relative to control subjects indicating the potential for biological impact. Systemic and local (oral mucosal) immune responses in acutely infected HIV individuals before the initiation of HAART have not been well characterized. Protein microarrays were used to analyze saliva and plasma from HIV infected and HIV uninfected subjects to identify new biomarkers for HIV disease progression and pathogenesis.

2011-09-08 | E-GEOD-24064 | biostudies-arrayexpress

Transcriptional profiling of antigen-responding CD4 T cells from PLWH to antigenic stimulation or global T cell activation

Project description:Despite antiretroviral therapy (ART), HIV-1 persists in latently-infected CD4+ T cells, preventing cure. Antigen (Ag) drives proliferation of infected cells, preventing latent reservoir decay. However, the relationship between antigen recognition and HIV-1 gene expression is poorly understood since most studies of latency reversal use agents that induce non-specific global T cell activation. Here, we isolated rare CD4+ T cells responding to cytomegalovirus (CMV) or HIV-1 Gag antigens from participants on long-term ART and assessed T cell activation and HIV-1 RNA expression upon co-culture with autologous dendritic cells (DCs) presenting cognate antigens. Physiological presentation of cognate antigens induced broad T cell activation (median 42-fold increase in CD154+CD69+ cells) and significantly increased HIV-1 transcription (median 4-fold), mostly through the induction of rare cells with higher viral expression. Thus, despite low proviral inducibility, physiologic antigen recognition can promote HIV-1 expression, potentially contributing to spontaneous reservoir activity on ART and viral rebound upon ART interruption. Additionally, we observed striking differences in the transcriptome profiles of Ag-responding CD4+ T cells after stimulations with Ag or global T cell activators. This analysis revealed quantitative differences between NFAT and NFkB target genes and may guide future approaches to Ag-mediated HIV-1 latency reversal.

2024-08-07 | GSE273898 | GEO

Transcriptome analysis of primary monocytes from HIV+ patients with differential responses to therapy

Project description:This study aimed at investigating the monocytic transcriptome distinction between patients with sustained virus suppression (BDL) and patients with virological failure during highly active antiretroviral therapy (HAART). This study provides the first transcriptomic distinctions in monocytes between viremic patients and BDLs on HAART. Our results reflected the outcome balanced between subversion of monocyte transcriptome by HIV and compensatory effect adapted by host cells. Total RNA obtained from primary monocytes from five HIV+ patients on HAART who sustainably controlled HIV below detection level (BDL), five HIV+ patients on HAART who consecutively experienced viremia and four healthy HIV sero-negative controls were compared against each other.

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