Sex Differences in Epigenetic Ageing for Older People Living with HIV
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PROVIDER: PRJNA1194131 | ENA |
REPOSITORIES: ENA
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Project description:Genome-wide DNA methylation profiling of blood samples from people living with HIV HIV-1 infection impacts biological ageing, and epigenetic clocks highlight epigenetic age acceleration in people with HIV. Despite evidence indicating sex differences in clinical, immunological, and virological measures, females have been underrepresented in most HIV epigenetic studies. Hence, we generated a more representative epigenetic dataset to examine sex differences in epigenetic ageing and relationships to clinical phenotypes.
2025-03-05 | GSE283506 | GEO
Project description:In this study we performed data-independet mass-spectrometry analysis of blood plasma collected from a cohort consisting of people living with HIV-1, people living with HIV-2, and HIV seronegative individuals. The data was used to infer signs of damage to a wide array of tissues and cell types.
2024-02-16 | PXD045155 | Pride
Project description:Immune activation in people living with HIV on anti-retroviral therapy is associated with increased risk of morbidity and mortality, but the underlying mechanisms are poorly understood. To identify whether perturbation of immunological pathways persist at systems level, we compared genome-wide whole blood transcriptomes from 26 people living with HIV on long-term anti-retroviral therapy with 12 HIV-negative healthy controls. All participants were Caucasian male adults recruited from London, UK. People living with HIV were on anti-retroviral therapy for a median of 8.5 years (interquartile range 3-16 years). They had undetectable plasma HIV viral load (<40 copies/ml) and median circulating CD4 counts of 703 cells/µl (interquartile range 491-841 cells/µl).
2021-02-26 | E-MTAB-8891 | biostudies-arrayexpress
Project description:BackgroundHIV-1 infection impacts biological ageing, and epigenetic clocks highlight epigenetic age acceleration in people with HIV. Despite evidence indicating sex differences in clinical, immunological, and virological measures, females have been underrepresented in most HIV epigenetic studies. Hence, we generated a more representative epigenetic dataset to examine sex differences in epigenetic ageing and relationships to clinical phenotypes and proteomics.MethodsWe calculated first, second, and third-generation epigenetic ages using DNA methylation data in an observational cohort of 52 females and 106 males with HIV age 50 and over. We profiled plasma biomarkers with Olink high-throughput proteomics to test associations with epigenetic age acceleration. Survival was ascertained over 5 years.FindingsEpigenetic age acceleration measured by three principal-component based chronological epigenetic age clocks (p = 0.0029, 0.021, 0.010) and one epigenetic mortality risk clock was significantly lower in females living with HIV compared to males (p = 0.0011). Additionally, sex was significantly associated with epigenetic biomarker scores for proportion of naïve CD4+ T cells (p = 0.0006), physical fitness including DNAmGait (p = 0.0010), DNAmGrip (p < 0.0001), and DNAmV02 max (p < 0.0001). We found epigenetic age acceleration associated with plasma proteomic markers involved in inflammation, senescence, immune regulation, kidney function, and tissue homoeostasis (p < 0.0001). Higher epigenetic frailty risk scores were associated with lower CD4 T cell counts (p = 0.0072) and lower CD4/CD8 ratio (p = 0.0017). Slower gait (p = 0.0017), greater frailty (p = 0.0074), and history of smoking (p = 0.042) were associated with increased DNAmFitAge. Risk of death was increased in females with PCPhenoAge acceleration over a 5-year timespan compared to men with PCPhenoAge acceleration (p = 0.03).InterpretationThese results highlight the importance of studying sex-specific differences in epigenetic ageing biomarkers for HIV-related geroscience research.FundingNational Institute on Aging (K23AG072960), National Center for Advancing Translational Sciences (UL1TR000457), National Institute of Mental Health (R21 MH115821).
| S-EPMC11849644 | biostudies-literature
Project description:The differential expression of metabolic genes between effector and exhausted CD8+ Tcells has been characterized in the people living with HIV (PLWH) using 768 genes from the NanoString Human Metabolic Pathways Panel.
2024-07-01 | GSE270720 | GEO
Project description:Understanding the evolution of broadly neutralizing antibody (bNAb) activity in people living with HIV is crucial for vaccine design and immunization strategies. It has been proposed that antibody cross-reactive activity is associated with lower CD4+ T cell counts during people living with HIV, but the underlying mechanisms remain unclear. To further explore the correlation between antibody reactivity and CD4+ T cell counts, we recruited people living with HIV with varying CD4+ T cell counts: (i) CD4+ T cell <= 50 cells/mL, (ii) 50 cells/mL < CD4+ T cell <= 200 cells/mL, (iii) 200 cells/mL < CD4+ T cell <= 500 cells/mL, (iv) 500 cells/mL < CD4+ T cell. We constructed four SOSIPs.664 trimers and evaluated the antigen-specific antibodies in serum. Immune repertoire sequencing was used to characterize the BCR repertoire of these individuals. The evaluation of antigen-specific antibodies with different SOSIP.664 trimers showed enhanced reactivity in individuals with low CD4+ T cell counts compared to those with high/normal CD4+ T cell counts. Analysis of antibody gene repertoires through BCR high throughput sequencing revealed an increased proportion of IgG with heavy chain complementarity-determining region 3 (CDRH3) loops exceeding 20 amino acids in individuals with CD4+ T cell counts below 50 cells/mL. Notably, the IGHV1-46 and IGHV4-34 germlines, which result in most polyreactive B cells, were preferentially used in individuals with low CD4+ T cell counts. These results suggest that limited engagement of CD4+ T cells could facilitate the survival of aberrant B cell repertoire with long CDRH3 regions.
2025-09-30 | GSE287663 | GEO
Project description:Myeloid dendritic cells (mDC) were isolated from antiretroviral therapy (ARV)-treated and untreated people living with HIV (PLWH), and from HIV uninfected Individuals. The results indicate that mDC are altered in genes expression from PLWH. Some RNA transcriptional changes are not completely restored by ARV. This provides more data on myeloid cells, an understudied cell type, and alterations in PLWH.
2020-01-10 | GSE139559 | GEO
Project description:Aminobisphosphonates reactivate the latent reservoir in people living with HIV-1
| PRJNA931626 | ENA
Project description:Background: Although acquired immunodeficiency syndrome-related mortality has decreased since the introduction of antiretroviral therapy, the incidence of lung cancer in patients living with HIV (PLWH) remains high. Understanding the effects of tobacco smoke on airway gene expression in PLWH may provide insight into the elevated lung cancer risk associated with HIV. Methods: Airway epithelial brushings were collected from 12 PLWH who smoke and 19 PLWH who have never smoked and profiled using RNA-seq. Linear models were used to identify genes differentially expressed between people who smoke and have never smoked and between people who previously smoked and have never smoked. Gene set enrichment analysis was used to validate smoking-related gene signatures across datasets. Data was integrated with gene expression data from a cohort of patients without HIV to identify genes differentially modulated by both smoking and HIV status. Results: We found that previous smoking-related gene signatures are similarly associated with smoking in PLWH, including the persistent differential expression of a subset of "irreversibly altered" genes in people who previously smoked compared to people who have never smoked. We also identified and validated two gene signatures specifically modulated in people who smoke without HIV. Conclusions: Many of the effects of smoking on bronchial gene expression are shared between PLWH and non-HIV individuals. Of the subset of genes that differ between PLWH and non-HIV individuals, it appears that the effect of smoking on gene expression is more attenuated in PLWH. This includes genes related to oxidative stress and epithelial integrity, and suggests potential mechanisms that may contribute to smoking-related outcomes that are more prevalent in PLWH, such as lung cancer.
2026-02-05 | GSE318533 | GEO
Project description:Persisting immune dysfunction in people living with HIV (PLHIV) on suppressive antiretroviral therapy (ART) is a key challenge to finding a cure for HIV. We investigated pomalidomide, a well-tolerated immunomodulatory drug, as an agent to enhance HIV-directed immune responses. We collected peripheral blood mononuclear cells (PBMC) from PLHIV on ART, cultured these in the presence of HIV peptides and found that pomalidomide significantly expanded tetramer-positive HIV-specific CD8+ T-cells with reduced markers of exhaustion and enhanced CD8+ T-cell-mediated killing of HIV-target cells. This was associated with an upregulation of carbon metabolism and cell cycle pathways, with MYB and BATF3 implicated as key regulators of the pomalidomide-mediated response. Pomalidomide also enhanced NK cell cytotoxicity against K562 as well as HIV-infected target cells by expanding polyfunctional cytotoxic NK cells. Given its immune-enhancing potential and good safety profile, pomalidomide should be further investigated as a therapeutic strategy for HIV control and cure.
2025-12-09 | GSE244148 | GEO