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Immunol."],"abstract":"<jats:p>Nearly 2.3 million individuals worldwide are coinfected with human immunodeficiency virus (HIV) and hepatitis C virus (HCV). Odds of HCV infection are six times higher in people living with HIV (PLWH) compared to their HIV-negative counterparts, with the highest prevalence among people who inject drugs (PWID) and men who have sex with men (MSM). HIV coinfection has a detrimental impact on the natural history of HCV, including higher rates of HCV persistence following acute infection, higher viral loads, and accelerated progression of liver fibrosis and development of end-stage liver disease compared to HCV monoinfection. Similarly, it has been reported that HCV coinfection impacts HIV disease progression in PLWH receiving anti-retroviral therapies (ART) where HCV coinfection negatively affects the homeostasis of CD4<jats:sup>+<\/jats:sup> T cell counts and facilitates HIV replication and viral reservoir persistence. While ART does not cure HIV, direct acting antivirals (DAA) can now achieve HCV cure in nearly 95% of coinfected individuals. However, little is known about how HCV cure and the subsequent resolution of liver inflammation influence systemic immune activation, immune reconstitution and the latent HIV reservoir. In this review, we will summarize the current knowledge regarding the pathogenesis of HIV\/HCV coinfection, the effects of HCV coinfection on HIV disease progression in the context of ART, the impact of HIV on HCV-associated liver morbidity, and the consequences of DAA-mediated HCV cure on immune reconstitution and HIV reservoir persistence in coinfected patients.<\/jats:p>","DOI":"10.3389\/fimmu.2021.726419","type":"journal-article","created":{"date-parts":[[2021,8,12]],"date-time":"2021-08-12T06:37:58Z","timestamp":1628750278000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":104,"title":["A Tale of Two Viruses: Immunological Insights Into HCV\/HIV Coinfection"],"prefix":"10.3389","volume":"12","author":[{"given":"Samaa T.","family":"Gobran","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Petronela","family":"Ancuta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naglaa H.","family":"Shoukry","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,8,12]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.317.7156.424","article-title":"HIV and Hepatitis C Among Injecting Drug Users","volume":"317","author":"Coutinho","year":"1998","journal-title":"BMJ (Clin Res Ed)"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1097\/QAD.0000000000000834","article-title":"Incidence of Sexually Transmitted Hepatitis C Virus Infection in HIV-Positive Men Who Have Sex With Men","volume":"29","author":"Hagan","year":"2015","journal-title":"Aids"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1002\/jia2.25348","article-title":"Sexually Transmitted Hepatitis C Virus Infections: Current Trends, and Recent Advances in Understanding the Spread in Men Who Have Sex With Men","volume":"22","author":"Nijmeijer","year":"2019","journal-title":"J Int AIDS Soc"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1086\/515315","article-title":"Perinatal Transmission of Hepatitis C Virus From Human Immunodeficiency Virus Type 1-Infected Mothers","volume":"177","author":"Thomas","year":"1998","journal-title":"Women Infants Transm Study J Infect Dis"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1034\/j.1600-0412.2003.00107.x","article-title":"Prospective Study of Mother-to-Infant Transmission of Hepatitis C Virus: A 10-Year Survey (1990-2000)","volume":"82","author":"Ferrero","year":"2003","journal-title":"Acta Obstet Gynecol Scand"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.2217\/fvl.13.11","article-title":"Viral Hepatitis in Resource-Limited Countries and Access to Antiviral Therapies: Current and Future Challenges","volume":"8","author":"Lemoine","year":"2013","journal-title":"Future Virol"},{"key":"B7","doi-asserted-by":"publisher","first-page":"797","DOI":"10.1016\/S1473-3099(15)00485-5","article-title":"Prevalence and Burden of HCV Co-Infection in People Living With HIV: A Global Systematic Review and Meta-Analysis","volume":"16","author":"Platt","year":"2016","journal-title":"Lancet Infect Dis"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1038\/nrgastro.2014.17","article-title":"HCV and HIV Co-Infection: Mechanisms and Management","volume":"11","author":"Chen","year":"2014","journal-title":"Nat Rev Gastroenterol Hepatol"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1097\/QAD.0000000000001203","article-title":"Virologic and Immunologic Aspects of HIV-Hepatitis C Virus Coinfection","volume":"30","author":"Chew","year":"2016","journal-title":"AIDS (Lond Engl)"},{"key":"B10","doi-asserted-by":"publisher","first-page":"e0187095","DOI":"10.1371\/journal.pone.0187095","article-title":"Peripheral Blood HIV-1 DNA Dynamics in Antiretroviral-Treated HIV\/HCV Co-Infected Patients Receiving Directly-Acting Antivirals","volume":"12","author":"Rozera","year":"2017","journal-title":"PloS One"},{"key":"B11","doi-asserted-by":"publisher","first-page":"ofaa115","DOI":"10.1093\/ofid\/ofaa115","article-title":"Hepatitis C Virus (HCV) Clearance After Treatment With Direct-Acting Antivirals in Human Immunodeficiency Virus (HIV)-HCV Coinfection Modulates Systemic Immune Activation and HIV Transcription on Antiretroviral Therapy","volume":"7","author":"Ghiglione","year":"2020","journal-title":"Open Forum Infect Dis"},{"key":"B12","volume-title":"Hepatitis C - 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