{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T03:03:13Z","timestamp":1793674993854,"version":"4.5.1"},"reference-count":78,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2021,12,29]],"date-time":"2021-12-29T00:00:00Z","timestamp":1640736000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Chronic hepatitis C virus (HCV) infection is associated with na\u00efve CD4+ T cell lymphopenia and long-standing\/persistent elevation of cellular and soluble immune activation parameters, the latter heightened in the setting of HIV co-infection. The underlying mechanisms are not completely understood. However, we recently reported that accelerated peripheral cell death may contribute to na\u00efve CD4+ T cell loss and that mechanistic relationships between monocyte activation, T cell activation, and soluble inflammatory mediators may also contribute. Chronic HCV infection can be cured by direct-acting anti-viral (DAA) therapy, and success is defined as sustained virological response (SVR, undetectable HCV RNA (ribonucleic acid) at 12 weeks after DAA treatment completion). However, there is no general consensus on the short-term and long-term immunological outcomes of DAA therapy. Here, we consolidate previous reports on the partial normalization of na\u00efve CD4+ lymphopenia and T cell immune activation and the apparent irreversibility of monocyte activation following DAA therapy in HCV infected and HCV\/HIV co-infected individuals. Further, advanced age and cirrhosis are associated with delayed or abrogation of immune reconstitution after DAA therapy, an indication that non-viral factors also likely contribute to host immune dysregulation in HCV infection.<\/jats:p>","DOI":"10.3390\/v14010050","type":"journal-article","created":{"date-parts":[[2021,12,29]],"date-time":"2021-12-29T23:31:35Z","timestamp":1640820695000},"page":"50","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Variable Normalization of Na\u00efve CD4+ Lymphopenia and Markers of Monocyte and T Cell Activation over the Course of Direct-Acting Anti-Viral Treatment of Chronic Hepatitis C Virus Infection"],"prefix":"10.3390","volume":"14","author":[{"given":"Ann W. N.","family":"Auma","sequence":"first","affiliation":[{"name":"Department of Pathology, Case Western Reserve University, Cleveland, OH 44106, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6908-1246","authenticated-orcid":false,"given":"Carey L.","family":"Shive","sequence":"additional","affiliation":[{"name":"Department of Pathology, Case Western Reserve University, Cleveland, OH 44106, USA"},{"name":"Cleveland VA Medical Center, Cleveland, OH 44106, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lenche","family":"Kostadinova","sequence":"additional","affiliation":[{"name":"Cleveland VA Medical Center, Cleveland, OH 44106, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donald D.","family":"Anthony","sequence":"additional","affiliation":[{"name":"Department of Pathology, Case Western Reserve University, Cleveland, OH 44106, USA"},{"name":"Cleveland VA Medical Center, Cleveland, OH 44106, USA"},{"name":"Metro Health Medical Center, Division of Rheumatology, Cleveland, OH 44106, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,12,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"ofab079","DOI":"10.1093\/ofid\/ofab079","article-title":"T-cell Activation Is Correlated with Monocyte Activation in HCV\/HIV Coinfection and Declines During HCV Direct-Acting Antiviral Therapy","volume":"8","author":"Auma","year":"2021","journal-title":"Open Forum Infect. 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