Biology subjects

Delporte, M.

Publications and source records attributed to Delporte, M..

5 recordsLinked to original sources

bioRxiv2026

Biological aging and comorbidities are linked to HIV 1 reservoir size despite suppressive antiretroviral therapy

Background The HIV reservoir persists in long-living immune cells after antiretroviral therapy initiation. Proviral DNA integrates at preferential host DNA sites, while HIV transcription continues under treatment, with potential biological consequences. Treated people with HIV remain at increased risk for premature aging and non-AIDS comorbidities compared to people without HIV. Whether HIV reservoir size and activity impact health outcomes during treatment remains unclear. Methods We analyzed 1895 people with HIV using antiretroviral therapy from the 2000HIV cohort to study associations between the reservoir and historic and prospective virologic and immunological response markers, comorbidity outcomes and biological aging scores. The reservoir was assessed by quantifying total and intact proviral HIV DNA in circulating CD4+ T cells, along with measures of HIV transcriptional activity, including cell-associated HIV RNA. Results HIV reservoir markers were highly correlating and associated with older aging scores and adverse virologic outcomes, including quantifiable and residual viremia at study entry and during follow-up. Total HIV DNA, unlike the minor fraction of intact HIV DNA, correlated with prevalent cardiovascular disease, subclinical atherosclerotic disease, liver fibrosis and incident malignancies independent of circulating inflammatory markers and lowest CD4 nadir. Total HIV RNA associated with prevalent cardiovascular disease and liver fibrosis. Conclusion The HIV reservoir associated with older aging scores and long-term health outcomes in people with HIV using antiretroviral therapy, independent of inflammation and immune suppression history. Whether reservoir-reducing interventions lower the risk of non-AIDS comorbidities should be studied in people with high reservoir markers. Funding and trial registration ViiV Healthcare; 2000HIV ClinicalTrials.gov number: NTC03994835

immunology↗

bioRxiv2026

An eicosanoid-enriched follicular microenvironment shapes germinal centre immune dynamics in antiretroviral-treated PLWH

Delineating the follicular (F) cellular and molecular landscape in HIV infection is essential for understanding neutralizing antibody responses and HIV reservoir maintenance. Multiplex imaging analysis revealed a less differentiated profile for follicular helper CD4 T cells (TFH) and significantly increased follicular CD25lo/hiFoxp3hi T cells in lymph nodes (LNs) from antiretroviral treated (cART) compared to viremic (Vir) people living with HIV (PLWH). Spatial transcriptomics identified distinct inflammatory follicular microenvironments in Vir and cART LNs, characterized by interferon and eicosanoid enrichment, respectively. In an independent cohort, scRNA-sequencing analysis of LN-derived cells revealed an enrichment of eicosanoid-related pathways in follicular immune cell types in non-neutralizers compared to neutralizers PLWH. In vitro infection and in situ multimodal investigation of HIV DNA+ cell microenvironments suggested a potential role of PGE2/Eicosanoids in maintaining viral reservoirs in cART LNs. Our data highlight cellular and molecular factors that could regulate both antibody responses and viral reservoir persistence in PLWH.

immunology↗

bioRxiv2026

Multi-Omics Clustering Differentiates the Total and Intact HIV Reservoirs and Related Host Immune Mechanisms

HIV reservoirs are heterogeneous across individuals, yet host determinants of this variability remain unclear. Applying multi-omics clustering to 1,230 people with HIV, integrating omics and functional data from circulating immune cells (transcriptomics, DNA methylation, immune phenotyping, ex-vivo cytokine production capacity), plasma proteomics, and CD4+ T-cell reservoir measurements (total and intact HIV-DNA copies), revealed three immunologically distinct endotypes: All Low (low total/low intact reservoir size), All High (high total/high intact reservoir size) and Mixed (high total/low intact reservoir size). Per endotype, distinct immune landscapes were noticed in single-layer analyses as well as differences in clinical signatures. Applying non-linear machine learning across all layers, key predictors not captured by linear single-layer approaches showed IFN-{gamma} production and TCF7/AK5 expression across T-cell and NK-cell populations as well as IL-1{beta}/MCP-1 production after 24h stimulation and MAN1C1/EDAR expression on T-cell populations, linked to intact and total reservoir size, respectively. This host-virus integrative multi-omics framework provides a systems-level resource that may help to personalize reservoir-reducing intervention studies aiming for HIV cure and/or comorbidity reductions. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=111 SRC="FIGDIR/small/734029v4_ufig1.gif" ALT="Figure 1"> View larger version (37K): org.highwire.dtl.DTLVardef@16fded7org.highwire.dtl.DTLVardef@18f2e69org.highwire.dtl.DTLVardef@12ffc9borg.highwire.dtl.DTLVardef@17127cc_HPS_FORMAT_FIGEXP M_FIG a) Multi-omics clustering of 1,230 virally suppressed PLHIV identified three immunologically distinct endotypes: All Low (n=428), Mixed (n=483), and All High (n=280), with distinct total and intact HIV reservoir sizes. b) Single-layer analyses reveal characteristic immune landscapes: All Low Th1-skewed, naive T cells (immunophenotyping), high IFN-{gamma} production (7-day), downregulated Type I IFN pathways (bulk transcriptome); Mixed intermediate Th1/Th2, CD8 and CD4 effector memory T cells (immunophenotyping), IL-5 production (7-day), downregulated Type I IFN pathways (bulk transcriptome); All High Th2-skewed, CD4 effector memory T cells (immunophenotyping), high IL-5 production (7-day), upregulated Type I IFN pathways (bulk transcriptome). c) Endotypes carry distinct comorbidity burdens: All Low lower carotid plaque, AIDS-defining malignancies, and residual viremia; Mixed intermediate burden; All High highest carotid plaque, AIDS-defining malignancies, opportunistic infections, and residual viremia. d) Non-linear classification models (XGBoost) prioritize top host predictive markers: IFN-{gamma} response (7-day), TCF7 and AK5 expression in CD4/CD8 T-cells and NK-cells (characterize All Low; IL-1 response (24-hour), MAN1C1 and EDAR in CD4/CD8 T-cells, and MCP1 response (24-hour) characterize All High. Created in BioRender. C_FIG

immunology↗

bioRxiv2026

Viral persistence and antiretroviral therapy shape systemic immune aging in treated HIV infection

Chronic infections can reshape immune system homeostasis, yet how persistent viral infections influence immune aging remains poorly understood. People living with HIV provide a unique model to investigate how long-term viral persistence affects immune aging despite effective antiretroviral therapy. Here, we characterize immune aging by integrating plasma proteomics with epigenetic and transcriptional profiles of circulating immune cells across large cohorts of treated individuals with HIV. We find that immune aging is markedly accelerated compared with healthy individuals and parallels established DNA methylation-based aging clocks. Accelerated immune aging is strongly associated with signatures of immunosenescence and correlates with the size of the latent HIV reservoir, suggesting a persistent imprint of viral persistence on immune aging trajectories. Notably, exposure to specific antiretroviral agents, particularly nucleoside reverse transcriptase inhibitors, is associated with reduced immune aging and suppression of age-associated immune gene programs. Together, these findings identify chronic viral persistence as a driver of systemic immune aging and indicate that antiretroviral therapy can partially modulate immune aging programs.

immunology↗

bioRxiv2023

Integrative assessment of total and intact HIV-1 reservoir by a five-region multiplexed Rainbow digital PCR assay

Persistent latent reservoirs of intact HIV-1 proviruses, capable of rebounding despite suppressive ART, hinder efforts towards an HIV-1 cure. Hence, assays specifically quantifying intact proviruses are crucial to assess the impact of curative interventions. Clinical trials have utilized two recent assays: intact proviral DNA assay (IPDA) and Q4PCR. While IPDA is more sensitive due to amplifying short fragments, it may overestimate intact fractions by relying only on two small regions. Q4PCR is sequencing-based and its performance might be subjected to bias against full-length proviruses. Leveraging digital PCR (dPCR) advancements, we developed the Rainbow 5-plex proviral HIV-1 DNA assay, assessing it with standard materials and samples from 69 PLWH. The Rainbow assay proved equally sensitive but more specific than IPDA, is not subjected to bias against full-length proviruses, enabling high-throughput quantification of total and intact reservoir size. This innovation offers potential for targeted evaluation and monitoring of rebound-competent reservoirs, contributing to HIV-1 management and cure strategies. TeaserThe 5 color HIV-1 Rainbow digital PCR assay offers a multi-level view on the HIV reservoir in one snapshot reaction.

molecular biology↗