Paradoxical CD4 decline on ART: a novel, rare and perplexing immunologic outcome
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE125223 | GEO | 2020/01/31
REPOSITORIES: GEO
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Project description:Paradoxical CD4 decline on ART: a novel, rare and perplexing immunologic outcome
| PRJNA515603 | ENA
Project description:A paired analysis of peripheral blood mononuclear cells (PBMCs) isolated before and after antiretroviral therapy (ART) from a robust number of HIV-infected patients (N=36). Results identify a total of 4,157 DEGs following ART in HIV-infected participants and the transition from a period of active virus replication before ART to one of viral suppression This study evaluated PBMC gene expression in cells from 36 (4 dropped from analysis) recently HIV-infected individuals to identify differentially expressed genes following 48 weeks of ART
2013-09-10 | E-GEOD-44228 | biostudies-arrayexpress
Project description:The virus-specific CD4+ T cell dysfunction associated with failure to control chronic infections is poorly understood in humans. An issue of critical clinical relevance is the lack of restoration of effective anti-HIV immunity after suppressive ART: viral rebound is the rule after cessation of therapy. Whether persistent HIV-specific CD4+ T cell dysfunction on ART contribute to this failed response is an important, yet unresolved, question. To decipher the consequences of ongoing viral antigen exposure, versus the results of durable cell-fate decision programs that would persist in former CP individuals after successful viral suppression on ART, we compared trancriptional profiles of chronic progressor before and after the initiation of ART, with the transcriptional profiles of elite controllers, HIV-infected individuals that spontaneously control viral load. Suppression of viremia by ART resulted in a distinct transcriptional landscape, with reduction in TFH gene expression but no correction of the TH1, TH17 and TH22 gene levels compared to the elite controller profile.
2019-07-15 | GSE128296 | GEO
Project description:Genome-wide DNA methylation profiling of monocytes and CD4+ T cells during acute HIV infection and following ART.
2021-07-15 | GSE180130 | GEO
Project description:The development of biomarkers that can predict viral rebound following discontinuation of antiretroviral therapy (ART) in HIV-1-infected humans would be an important advance in HIV-1 cure research. In a prior study, we initiated ART in 20 rhesus macaques on days 0, 1, 2, and 3 following SIVmac251 infection prior to plasma viremia1. Following 6 months of suppressive ART, we discontinued ART and observed viral rebound in 9 of 20 animals. Here we show that transcriptomic and proteomic signatures of inflammation and immune activation in peripheral blood during ART suppression predicted viral rebound following ART discontinuation. Higher levels of proinflammatory and cellular immune activation pathways, including TNF, IL-1, IL-6, monocyte, and T cell activation signaling pathways, correlated with viral rebound following ART discontinuation. Immune modulatory IL-10 and TGF-b signaling also correlated with viral rebound. We then validated these candidate biomarkers of viral rebound in a second cohort of SIV-infected, ART-suppressed macaques. Taken together, these data suggest that persistent upregulation of inflammatory and immune activation pathways despite suppressive ART may represent a peripheral blood biomarker signature of the rebound-competent viral reservoir. The development of interventions that target the viral reservoir and modulate this signature may open new avenues in HIV-1 cure research.
2023-08-30 | GSE203603 | GEO
Project description:Patterns of expressed genes examined in cryopreserved peripheral blood mononuclear cells (PBMCs) of seropositive persons electing to stop antiretroviral therapy in the AIDS Clinical Trials Group Study A 5170, were scrutinized to identify markers capable of predicting the likelihood of CD4+ T cell depletion after cessation of ART. Two cohorts were matched for clinical characteristics in a study of the effects of therapy interruption (TI) in ART-treated patients with immunological preservation. Disease progression was determined by CD4+ T cell count decline 24 weeks after TI.Gene Set Enrichment Analysis (GSEA) identified a set of genes in the Ras signaling pathway, associated with the downregulation of apoptosis, as significantly upregulated in the good outcome group at cessation of ART. Experiment Overall Design: There are 96 samples in this study. 24 patients with good outcome results and 24 matched patients with poor outcome results. Each patient has two time points: week0 and week 24
2008-04-04 | E-GEOD-10924 | biostudies-arrayexpress
Project description:Background. HIV-infected individuals on antiretroviral therapy (HIV/ART) experience higher levels of non-AIDS morbidity than uninfected people, which is believed to be driven by inflammation that persists despite viral suppression. Elevations in plasma cytokines, coagulation markers and both innate and adaptive immune cell activation during untreated infection are often incompletely reversed by ART and associated with these morbidities. Monocytes/macrophages play a central role in many of these complications including neurocognitive and cardiovascular disease. Results. We investigated monocyte surface markers, gene expression and plasma cytokines in 11 HIV-infected older individuals (median age 53 years) who started therapy with low CD4 counts (median 129 cells/ul), with elevated hsCRP (≥2mg/L) despite long-term ART (median 7.4 years), along with age, gender, race and smoking status-matched controls. Major monocyte subsets (based on CD14/CD16/CD163) were not different from controls, but surface levels differed for CD163 (p=0.022), PD1 (p=0.015) and a trend for tissue factor (p=0.098). As a group, HIV/ART subjects had elevated levels of plasma CCL2 (MCP-1; p=0.0001), CXCL9 (MIG; p=0.04) and sIL2R (p=0.015), which were highly correlated, whereas sCD14 and several other markers were not significantly elevated. However, principal component analysis of soluble markers revealed that about half of HIV/ART subjects clustered with controls, whereas the remainder were distinct, driven by IL-10, CCL11, CXCL10, CXCL11 as well as CCL2, CXCL9 and sIL2R. Outlier subjects were significantly older than those who clustered with controls. Gene expression analysis unexpectedly revealed downregulation in HIV/ART monocytes of multiple genes linked to immune functions including inflammation, immune cell development and cell-cell signaling. Conclusions. These results reveal a novel pattern of immune dysregulation involving both aberrant inflammation and monocyte dysfunction, which suggests complex mechanisms linking monocytes and HIV/ART comorbidities.
2020-01-08 | GSE137438 | GEO
Project description:A paired analysis of peripheral blood mononuclear cells (PBMCs) isolated before and after antiretroviral therapy (ART) from a robust number of HIV-infected patients (N=36). Results identify a total of 4,157 DEGs following ART in HIV-infected participants and the transition from a period of active virus replication before ART to one of viral suppression
2013-09-10 | GSE44228 | GEO
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
Project description:Comparison of total RNA-seq data from ex vivo unstimulated and stimulated (with anti-CD3/CD28) cells from two primary cell models of HIV latency (resting-cell and wild-type virus models) and peripheral CD4+ T cells from HIV-infected ART-suppressed individuals (ex vivo cells). Two donors were analyzed per model.
2020-10-28 | GSE144585 | GEO