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        <identifier>oai:figshare.com:article/32390040</identifier>
        <datestamp>2026-09-28T07:59:50Z</datestamp>
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          <dc:title>Long-term antiviral therapy fails to resolve the persistent plasma cytokines and virome dysregulations in HIV-1 infection</dc:title>
          <dc:creator>Yingying Ma (18762652)</dc:creator>
          <dc:subject>Medical virology</dc:subject>
          <dc:subject>Viral Metagenomics data</dc:subject>
          <dc:subject>Anellovirus</dc:subject>
          <dc:subject>antiretroviral theraphy</dc:subject>
          <dc:description>&lt;p dir="ltr"&gt;In the era of antiretroviral therapy (ART), persistent immune activation and inflammation increase the risk of non-AIDS-related complications in people living with HIV (PLWH), representing a major challenge in AIDS treatment. HIV-1 infection disrupts cytokine network and plasma virome, yet the long-term impact of ART on them and their relationship with immune activation remain poorly understood. Here, we characterized the immune profiles and plasma virome in PLWH on ART for 5–20 years using metagenomic sequencing and multiplex immunoassays. Cytokines IL-10, VEGF, GM-CSF, GM-CSF, PDGF-BB, FGF basic and IL-1rα remained significantly elevated (5.3- to 27.9-fold), whereas IL-12 and IL-4 remained significantly decreased (1.4- to 2.6-fold) during long-term ART compared with healthy controls.&lt;b&gt; &lt;/b&gt;ART declined anellovirus abundance but increased the positive rate and abundance of human pegivirus 1 (HPgV-1). Specific anellovirus species strongly correlated with elevated IL-10, GM-CSF, and VEGF. Pooled anellovirus peptide library induced increased IFN-γ secretion in multiple immune cell subsets and promoted early Th1 cell activation. A combination of two anelloviruses and three cytokines showed strong power to discriminate immune non-responders (INR) from immune responders (IR).&lt;b&gt; &lt;/b&gt;These findings indicate that long-term ART does not fully restore the homeostasis of cytokine network and plasma virome in PLWH. Persistently elevated cytokines (e.g. IL-10 and VEGF) provide a plausible explanation for the high risk of non-AIDS-related comorbidities and represent potential intervention targets for adjunctive therapeutic strategies to improve immune recovery in PLWH.&lt;/p&gt;</dc:description>
          <dc:date>2026-09-28T07:59:50Z</dc:date>
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          <dc:identifier>10.6084/m9.figshare.32390040.v2</dc:identifier>
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          <dc:rights>CC BY 4.0</dc:rights>
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