Assessment of CD4+ T cell recovery after direct-acting antiviral hepatitis C treatment in HIV/HCV coinfected immunological nonresponders to ART
Aim: This study investigated the effects of successful hepatitis C virus (HCV) treatment with direct-acting antivirals (DAAs) on CD4+ T cell recovery in HIV/HCV coinfected immunological non-responders (INRs) to antiretroviral therapy (ART). The study assessed changes in CD4+ and CD8+ T cell counts,...
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Open Exploration Publishing Inc.
2025-05-01
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| Series: | Exploration of Medicine |
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| Online Access: | https://www.explorationpub.com/uploads/Article/A1001323/1001323.pdf |
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| author | Violetta Vlasova Evgeniya Saidakova Larisa Korolevskaya Nadezhda Shmagel Konstantin Shmagel |
| author_facet | Violetta Vlasova Evgeniya Saidakova Larisa Korolevskaya Nadezhda Shmagel Konstantin Shmagel |
| author_sort | Violetta Vlasova |
| collection | DOAJ |
| description | Aim: This study investigated the effects of successful hepatitis C virus (HCV) treatment with direct-acting antivirals (DAAs) on CD4+ T cell recovery in HIV/HCV coinfected immunological non-responders (INRs) to antiretroviral therapy (ART). The study assessed changes in CD4+ and CD8+ T cell counts, immune activation, inflammation, T cell exhaustion, and the size of the naïve CD4+ T cell pool following DAA therapy to determine whether HCV suppression enhances immune restoration in coinfected INRs. Methods: Three groups were analyzed: DAA-treated INRs (n = 9), untreated HIV/HCV coinfected INRs (n = 10), and healthy controls (n = 10). Plasma cytokine levels and viral loads were quantified using multiplex immunoassay and real-time PCR. Peripheral blood mononuclear cells were analyzed via flow cytometry to evaluate T cell subsets, activation (HLA-DR+CD38+), and exhaustion markers (PD-1, TIGIT). Results: Both INR groups showed significantly lower CD4+ T cell counts and elevated CD4+ T cell proliferation compared to controls, with no significant difference between DAA-treated and untreated patients. Deficits in naïve CD4+ T cells were observed in both INR groups but reached statistical significance only in untreated individuals. Activated CD4+ and CD8+ T cells and proinflammatory cytokines of IFN and IL-10 families remained elevated in INRs after DAA treatment. DAAs reduced PD-1 and TIGIT expression on CD4+ T cells, suggesting attenuated exhaustion, but did not alter exhausted T cell frequencies in CD4+ or CD8+ T cells. Conclusions: HCV coinfection in people living with HIV (PLWH) not only increases the risk of immunological non-response to ART but also has lasting impacts on the immune system. Even after successful HCV clearance with DAAs, INRs experience persistent immune dysregulation, including low CD4+ T cell counts, deficits in the naïve CD4+ T cell compartment, and ongoing inflammation. This indicates that HCV eradication alone is insufficient to reverse the long-term immune damage resulting from coinfection. |
| format | Article |
| id | doaj-art-fa1152ee27d0435fba9fc771dfa0160c |
| institution | OA Journals |
| issn | 2692-3106 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Open Exploration Publishing Inc. |
| record_format | Article |
| series | Exploration of Medicine |
| spelling | doaj-art-fa1152ee27d0435fba9fc771dfa0160c2025-08-20T02:26:00ZengOpen Exploration Publishing Inc.Exploration of Medicine2692-31062025-05-016100132310.37349/emed.2025.1001323Assessment of CD4+ T cell recovery after direct-acting antiviral hepatitis C treatment in HIV/HCV coinfected immunological nonresponders to ARTVioletta Vlasova0https://orcid.org/0000-0002-1656-7277Evgeniya Saidakova1https://orcid.org/0000-0002-4342-5362Larisa Korolevskaya2https://orcid.org/0000-0001-9840-7578Nadezhda Shmagel3https://orcid.org/0000-0002-2763-3620Konstantin Shmagel4https://orcid.org/0000-0001-6355-6178Institute of Ecology and Genetics of Microorganisms, Perm Federal Research Center, Ural Branch of the Russian Academy of Sciences, 614081 Perm, RussiaInstitute of Ecology and Genetics of Microorganisms, Perm Federal Research Center, Ural Branch of the Russian Academy of Sciences, 614081 Perm, RussiaInstitute of Ecology and Genetics of Microorganisms, Perm Federal Research Center, Ural Branch of the Russian Academy of Sciences, 614081 Perm, RussiaInstitute of Ecology and Genetics of Microorganisms, Perm Federal Research Center, Ural Branch of the Russian Academy of Sciences, 614081 Perm, RussiaInstitute of Ecology and Genetics of Microorganisms, Perm Federal Research Center, Ural Branch of the Russian Academy of Sciences, 614081 Perm, RussiaAim: This study investigated the effects of successful hepatitis C virus (HCV) treatment with direct-acting antivirals (DAAs) on CD4+ T cell recovery in HIV/HCV coinfected immunological non-responders (INRs) to antiretroviral therapy (ART). The study assessed changes in CD4+ and CD8+ T cell counts, immune activation, inflammation, T cell exhaustion, and the size of the naïve CD4+ T cell pool following DAA therapy to determine whether HCV suppression enhances immune restoration in coinfected INRs. Methods: Three groups were analyzed: DAA-treated INRs (n = 9), untreated HIV/HCV coinfected INRs (n = 10), and healthy controls (n = 10). Plasma cytokine levels and viral loads were quantified using multiplex immunoassay and real-time PCR. Peripheral blood mononuclear cells were analyzed via flow cytometry to evaluate T cell subsets, activation (HLA-DR+CD38+), and exhaustion markers (PD-1, TIGIT). Results: Both INR groups showed significantly lower CD4+ T cell counts and elevated CD4+ T cell proliferation compared to controls, with no significant difference between DAA-treated and untreated patients. Deficits in naïve CD4+ T cells were observed in both INR groups but reached statistical significance only in untreated individuals. Activated CD4+ and CD8+ T cells and proinflammatory cytokines of IFN and IL-10 families remained elevated in INRs after DAA treatment. DAAs reduced PD-1 and TIGIT expression on CD4+ T cells, suggesting attenuated exhaustion, but did not alter exhausted T cell frequencies in CD4+ or CD8+ T cells. Conclusions: HCV coinfection in people living with HIV (PLWH) not only increases the risk of immunological non-response to ART but also has lasting impacts on the immune system. Even after successful HCV clearance with DAAs, INRs experience persistent immune dysregulation, including low CD4+ T cell counts, deficits in the naïve CD4+ T cell compartment, and ongoing inflammation. This indicates that HCV eradication alone is insufficient to reverse the long-term immune damage resulting from coinfection.https://www.explorationpub.com/uploads/Article/A1001323/1001323.pdfhiv/hcv coinfectionimmunological non-responseantiretroviral therapydirect-acting antiviralsimmune restoration |
| spellingShingle | Violetta Vlasova Evgeniya Saidakova Larisa Korolevskaya Nadezhda Shmagel Konstantin Shmagel Assessment of CD4+ T cell recovery after direct-acting antiviral hepatitis C treatment in HIV/HCV coinfected immunological nonresponders to ART Exploration of Medicine hiv/hcv coinfection immunological non-response antiretroviral therapy direct-acting antivirals immune restoration |
| title | Assessment of CD4+ T cell recovery after direct-acting antiviral hepatitis C treatment in HIV/HCV coinfected immunological nonresponders to ART |
| title_full | Assessment of CD4+ T cell recovery after direct-acting antiviral hepatitis C treatment in HIV/HCV coinfected immunological nonresponders to ART |
| title_fullStr | Assessment of CD4+ T cell recovery after direct-acting antiviral hepatitis C treatment in HIV/HCV coinfected immunological nonresponders to ART |
| title_full_unstemmed | Assessment of CD4+ T cell recovery after direct-acting antiviral hepatitis C treatment in HIV/HCV coinfected immunological nonresponders to ART |
| title_short | Assessment of CD4+ T cell recovery after direct-acting antiviral hepatitis C treatment in HIV/HCV coinfected immunological nonresponders to ART |
| title_sort | assessment of cd4 t cell recovery after direct acting antiviral hepatitis c treatment in hiv hcv coinfected immunological nonresponders to art |
| topic | hiv/hcv coinfection immunological non-response antiretroviral therapy direct-acting antivirals immune restoration |
| url | https://www.explorationpub.com/uploads/Article/A1001323/1001323.pdf |
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