{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,2]],"date-time":"2025-11-02T03:41:28Z","timestamp":1762054888125,"version":"build-2065373602"},"reference-count":52,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2022,6,21]],"date-time":"2022-06-21T00:00:00Z","timestamp":1655769600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI15CIII\/00031","PI18CIII\/00020","RD16CIII\/0002\/0001","RD16CIII\/0002\/0002","CP14\/CIII\/00010","R01AI143567","57\/2016","57\/2017"],"award-info":[{"award-number":["PI15CIII\/00031","PI18CIII\/00020","RD16CIII\/0002\/0001","RD16CIII\/0002\/0002","CP14\/CIII\/00010","R01AI143567","57\/2016","57\/2017"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"name":"SPANISH AIDS Research Network","award":["PI15CIII\/00031","PI18CIII\/00020","RD16CIII\/0002\/0001","RD16CIII\/0002\/0002","CP14\/CIII\/00010","R01AI143567","57\/2016","57\/2017"],"award-info":[{"award-number":["PI15CIII\/00031","PI18CIII\/00020","RD16CIII\/0002\/0001","RD16CIII\/0002\/0002","CP14\/CIII\/00010","R01AI143567","57\/2016","57\/2017"]}]},{"name":"Miguel Servet program","award":["PI15CIII\/00031","PI18CIII\/00020","RD16CIII\/0002\/0001","RD16CIII\/0002\/0002","CP14\/CIII\/00010","R01AI143567","57\/2016","57\/2017"],"award-info":[{"award-number":["PI15CIII\/00031","PI18CIII\/00020","RD16CIII\/0002\/0001","RD16CIII\/0002\/0002","CP14\/CIII\/00010","R01AI143567","57\/2016","57\/2017"]}]},{"name":"National Institutes of Health (NIH)","award":["PI15CIII\/00031","PI18CIII\/00020","RD16CIII\/0002\/0001","RD16CIII\/0002\/0002","CP14\/CIII\/00010","R01AI143567","57\/2016","57\/2017"],"award-info":[{"award-number":["PI15CIII\/00031","PI18CIII\/00020","RD16CIII\/0002\/0001","RD16CIII\/0002\/0002","CP14\/CIII\/00010","R01AI143567","57\/2016","57\/2017"]}]},{"name":"FCT\u2014Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","award":["PI15CIII\/00031","PI18CIII\/00020","RD16CIII\/0002\/0001","RD16CIII\/0002\/0002","CP14\/CIII\/00010","R01AI143567","57\/2016","57\/2017"],"award-info":[{"award-number":["PI15CIII\/00031","PI18CIII\/00020","RD16CIII\/0002\/0001","RD16CIII\/0002\/0002","CP14\/CIII\/00010","R01AI143567","57\/2016","57\/2017"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background: Although human immunodeficiency virus type 1 (HIV-1) reservoir size is very stable under antiretroviral therapy (ART), individuals exposed to the Hepatitis C virus (HCV) (chronically coinfected and spontaneous clarifiers) show an increase in HIV reservoir size and in spliced viral RNA, which could indicate that the viral protein regulator Tat is being more actively synthesized and, thus, could lead to a higher yield of new HIV. However, it is still unknown whether the effect of HCV elimination with direct-acting antivirals (DAAs) could modify the HIV reservoir and splicing. Methods: This longitudinal study (48 weeks\u2019 follow-up after sustained virological response) involves 22 HIV+-monoinfected individuals, 17 HIV+\/HCV- spontaneous clarifiers, and 24 HIV+\/HCV+ chronically infected subjects who eliminated HCV with DAAs (all of them aviremic, viral load &lt; 50). Viral-spliced RNA transcripts and proviral DNA copies were quantified by qPCR. Paired samples were analyzed using a mixed generalized linear model. Results: A decrease in HIV proviral DNA was observed in HIV+\/HCV- subjects, but no significant differences were found for the other study groups. An increased production of multiple spliced transcripts was found in HIV+ and HIV+\/HCV+ individuals. Conclusions: We conclude that elimination of HCV by DAAs was unable to revert the consequences derived from chronic HCV infection for the reservoir size and viral splicing, which could indicate an increased risk of rapid HIV-reservoir reactivation. Moreover, spontaneous clarifiers showed a significant decrease in the HIV reservoir, likely due to an enhanced immune response in these individuals.<\/jats:p>","DOI":"10.3390\/jcm11133579","type":"journal-article","created":{"date-parts":[[2022,6,21]],"date-time":"2022-06-21T21:55:19Z","timestamp":1655848519000},"page":"3579","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Dynamics of HIV Reservoir and HIV-1 Viral Splicing in HCV-Exposed Individuals after Elimination with DAAs or Spontaneous Clearance"],"prefix":"10.3390","volume":"11","author":[{"given":"Paula","family":"Mart\u00ednez-Rom\u00e1n","sequence":"first","affiliation":[{"name":"Laboratory of Reference and Research on Viral Hepatitis, Centro Nacional de Microbiolog\u00eda, Instituto de Salud Carlos III, 28220 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Celia","family":"Crespo-Bermejo","sequence":"additional","affiliation":[{"name":"Laboratory of Reference and Research on Viral Hepatitis, Centro Nacional de Microbiolog\u00eda, Instituto de Salud Carlos III, 28220 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel","family":"Valle-Millares","sequence":"additional","affiliation":[{"name":"Laboratory of Reference and Research on Viral Hepatitis, Centro Nacional de Microbiolog\u00eda, Instituto de Salud Carlos III, 28220 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0015-5961","authenticated-orcid":false,"given":"Violeta","family":"Lara-Aguilar","sequence":"additional","affiliation":[{"name":"Laboratory of Reference and Research on Viral Hepatitis, Centro Nacional de Microbiolog\u00eda, Instituto de Salud Carlos III, 28220 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sonia","family":"Arca-Lafuente","sequence":"additional","affiliation":[{"name":"Laboratory of Reference and Research on Viral Hepatitis, Centro Nacional de Microbiolog\u00eda, Instituto de Salud Carlos III, 28220 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8102-4079","authenticated-orcid":false,"given":"Luz","family":"Mart\u00edn-Carbonero","sequence":"additional","affiliation":[{"name":"Instituto de Investigaci\u00f3n Sanitaria Hospital de la Paz (IdiPAZ), 28046 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4212-7419","authenticated-orcid":false,"given":"Pablo","family":"Ryan","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Infanta Leonor Hospital, 28031 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7073-5211","authenticated-orcid":false,"given":"Ignacio","family":"de los Santos","sequence":"additional","affiliation":[{"name":"Servicio de Medicina Interna-Infecciosas, Hospital Universitario de La Princesa, 28006 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mar\u00eda Rosa","family":"L\u00f3pez-Huertas","sequence":"additional","affiliation":[{"name":"Immunopathology Unit, Centro Nacional de Microbiolog\u00eda, Instituto de Salud Carlos III, 28220 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8148-0928","authenticated-orcid":false,"given":"Claudia","family":"Palladino","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy, Research Institute for Medicines (iMed.ULisboa), Universidade de Lisboa, 1649-003 Lisbon, Portugal"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mar\u00eda","family":"Mu\u00f1oz-Mu\u00f1oz","sequence":"additional","affiliation":[{"name":"Department of Animal Genetics, Instituto Nacional de Investigaci\u00f3n y Tecnnolog\u00eda Agraria y Alimentaria (INIA), 28040 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5110-2213","authenticated-orcid":false,"given":"Amanda","family":"Fern\u00e1ndez-Rodr\u00edguez","sequence":"additional","affiliation":[{"name":"Laboratory of Reference and Research on Viral Hepatitis, Centro Nacional de Microbiolog\u00eda, Instituto de Salud Carlos III, 28220 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6464-5770","authenticated-orcid":false,"given":"Mayte","family":"Coiras","sequence":"additional","affiliation":[{"name":"Immunopathology Unit, Centro Nacional de Microbiolog\u00eda, Instituto de Salud Carlos III, 28220 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2297-5098","authenticated-orcid":false,"given":"Ver\u00f3nica","family":"Briz","sequence":"additional","affiliation":[{"name":"Laboratory of Reference and Research on Viral Hepatitis, Centro Nacional de Microbiolog\u00eda, Instituto de Salud Carlos III, 28220 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"name":"on behalf of the COVIHEP network","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,6,21]]},"reference":[{"key":"ref_1","unstructured":"OMS (2022, February 22). 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