{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T23:39:10Z","timestamp":1792798750013,"version":"4.5.0"},"reference-count":49,"publisher":"American Society for Microbiology","issue":"12","license":[{"start":{"date-parts":[[2023,12,21]],"date-time":"2023-12-21T00:00:00Z","timestamp":1703116800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/doi.org\/10.1128\/ASMCopyrightv2"},{"start":{"date-parts":[[2023,12,21]],"date-time":"2023-12-21T00:00:00Z","timestamp":1703116800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"name":"Canadian HIV Trials Network"},{"name":"Gouvernement du Canada | Canadian Institutes of Health Research","award":["PJT-173467"],"award-info":[{"award-number":["PJT-173467"]}],"id":[{"id":"https:\/\/ror.org\/01gavpb45","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Gouvernement du Canada | Canadian Institutes of Health Research","award":["HOP-120239"],"award-info":[{"award-number":["HOP-120239"]}],"id":[{"id":"https:\/\/ror.org\/01gavpb45","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Gouvernement du Canada | Canadian Institutes of Health Research","award":["PJT-153052"],"award-info":[{"award-number":["PJT-153052"]}],"id":[{"id":"https:\/\/ror.org\/01gavpb45","id-type":"ROR","asserted-by":"crossref"}]},{"name":"FRQ | Fonds de Recherche du Qu\u00e9bec - Sant\u00e9","id":[{"id":"https:\/\/ror.org\/02eqrsj93","id-type":"ROR","asserted-by":"crossref"}]},{"name":"HHS | National Institutes of Health","award":["U19AI159819"],"award-info":[{"award-number":["U19AI159819"]}]},{"name":"Gouvernement du Canada | Canadian Institutes of Health Research","award":["FDN-143270"],"award-info":[{"award-number":["FDN-143270"]}],"id":[{"id":"https:\/\/ror.org\/01gavpb45","id-type":"ROR","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001804","name":"Canada Research Chairs","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100001804","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Virol"],"published-print":{"date-parts":[[2023,12,21]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    The human immunodeficiency virus (HIV) persists in HIV viral reservoirs despite antiretroviral therapy (ART). Hepatitis C virus (HCV) coinfection is associated with increased HIV reservoir size and residual HIV transcription during ART. Herein, we investigated the impact of direct acting antivirals (DAA)-mediated HCV cure on the size\/transcriptional activity of the HIV reservoirs and investigated predictors of HIV reservoirs decline in HCV+\/HIV+ coinfected individuals. HCV+\/HIV+ (\n                    <jats:italic>n<\/jats:italic>\n                    = 20) and HCV+\/HIV\u2212 (\n                    <jats:italic>n<\/jats:italic>\n                    = 14) participants were examined prior to DAA treatment (baseline), at the end of treatment (EOT), and at 12\u201324 weeks after EOT (follow-up). In HCV+\/HIV+ individuals, DAA-mediated HCV cure significantly reduced integrated HIV DNA levels, mainly in participants infected with HCV prior to HIV. Integrated HIV DNA, unspliced (US), and multiply spliced (MS) HIV RNA levels were quantified in sorted CD4+ T-cells. Despite the transient elevation of US HIV RNA at EOT, changes in US and MS HIV RNA were not statistically significant. Plasma inflammation markers were measured and DAA also reduced plasma sCD163 and sCD14. Changes in immunological\/virological parameters were analyzed using multivariate random forest analysis where pre-ART peak HIV viremia and HCV viral load predicted integrated HIV DNA and US RNA changes. In conclusion, we demonstrate the beneficial impact of DAA on HIV reservoirs and immune activation, with a fraction of HIV reservoirs being DAA-sensitive in people infected with HCV before HIV. Furthermore, we identify HIV\/HCV viremia as the top predictors of DAA-mediated changes in the HIV reservoirs. These findings support the need for early ART and DAA treatment in HIV\/HCV coinfections.\n                  <\/jats:p>\n                  <jats:sec>\n                    <jats:title>IMPORTANCE<\/jats:title>\n                    <jats:p>Antiretroviral therapy (ART) for human immunodeficiency virus (HIV) can control virus replication and prolong the life of people living with HIV (PLWH). However, the virus remains dormant within immune cells in what is called the HIV reservoir. Furthermore, 2.3 million PLWH are also coinfected with hepatitis C virus (HCV) and are at risk of developing chronic liver disease and cancer. HCV treatment with direct acting antivirals (DAA) can completely cure the infection in more than 95% of treated individuals and improve their long-term health outcomes. In this study, we investigated how HCV treatment and cure affect the HIV reservoir. We demonstrate the beneficial impact of DAA treatment as it reduces the HIV reservoirs in particular in people infected with HCV before HIV. These results support the need for early ART and DAA treatment in HIV\/HCV coinfections.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/jvi.01105-23","type":"journal-article","created":{"date-parts":[[2023,12,5]],"date-time":"2023-12-05T09:00:32Z","timestamp":1701766832000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":9,"title":["DAA-mediated HCV cure reduces HIV DNA levels in HCV\/HIV coinfected people"],"prefix":"10.1128","volume":"97","author":[{"given":"Samaa T.","family":"Gobran","sequence":"first","affiliation":[{"name":"D\u00e9partement de microbiologie, infectiologie, et immunologie, Universit\u00e9 de Montr\u00e9al, Facult\u00e9 de m\u00e9dicine, Montr\u00e9al, Qu\u00e9bec, Canada"},{"name":"Centre de Recherche du Centre hospitalier de l\u2019Universit\u00e9 de Montr\u00e9al (CRCHUM), Montr\u00e9al, Qu\u00e9bec, Canada"},{"name":"Department of Medical Microbiology and Immunology, Faculty of Medicine, Zagazig University, Zagazig, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Am\u00e9lie","family":"Pagliuzza","sequence":"additional","affiliation":[{"name":"Centre de Recherche du Centre hospitalier de l\u2019Universit\u00e9 de Montr\u00e9al (CRCHUM), Montr\u00e9al, Qu\u00e9bec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Omar","family":"Khedr","sequence":"additional","affiliation":[{"name":"Centre de Recherche du Centre hospitalier de l\u2019Universit\u00e9 de Montr\u00e9al (CRCHUM), Montr\u00e9al, Qu\u00e9bec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Augustine","family":"Fert","sequence":"additional","affiliation":[{"name":"D\u00e9partement de microbiologie, infectiologie, et immunologie, Universit\u00e9 de Montr\u00e9al, Facult\u00e9 de m\u00e9dicine, Montr\u00e9al, Qu\u00e9bec, Canada"},{"name":"Centre de Recherche du Centre hospitalier de l\u2019Universit\u00e9 de Montr\u00e9al (CRCHUM), Montr\u00e9al, Qu\u00e9bec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas","family":"Chomont","sequence":"additional","affiliation":[{"name":"D\u00e9partement de microbiologie, infectiologie, et immunologie, Universit\u00e9 de Montr\u00e9al, Facult\u00e9 de m\u00e9dicine, Montr\u00e9al, Qu\u00e9bec, Canada"},{"name":"Centre de Recherche du Centre hospitalier de l\u2019Universit\u00e9 de Montr\u00e9al (CRCHUM), Montr\u00e9al, Qu\u00e9bec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie","family":"Bruneau","sequence":"additional","affiliation":[{"name":"Centre de Recherche du Centre hospitalier de l\u2019Universit\u00e9 de Montr\u00e9al (CRCHUM), Montr\u00e9al, Qu\u00e9bec, Canada"},{"name":"D\u00e9partement de m\u00e9decine de famille et de m\u00e9decine d'urgence, Facult\u00e9 de m\u00e9decine, Universit\u00e9 de Montr\u00e9al, Montr\u00e9al, Qu\u00e9bec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina B.","family":"Klein","sequence":"additional","affiliation":[{"name":"Department of Medicine, Faculty of Medicine and Health Sciences, McGill University, Montr\u00e9al, Qu\u00e9bec, Canada"},{"name":"Department of Medicine, Division of Infectious Diseases, McGill University Health Center (MUHC), Montr\u00e9al, Qu\u00e9bec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1922-5640","authenticated-orcid":false,"given":"Petronela","family":"Ancuta","sequence":"additional","affiliation":[{"name":"D\u00e9partement de microbiologie, infectiologie, et immunologie, Universit\u00e9 de Montr\u00e9al, Facult\u00e9 de m\u00e9dicine, Montr\u00e9al, Qu\u00e9bec, Canada"},{"name":"Centre de Recherche du Centre hospitalier de l\u2019Universit\u00e9 de Montr\u00e9al (CRCHUM), Montr\u00e9al, Qu\u00e9bec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8817-8238","authenticated-orcid":true,"given":"Naglaa H.","family":"Shoukry","sequence":"additional","affiliation":[{"name":"Centre de Recherche du Centre hospitalier de l\u2019Universit\u00e9 de Montr\u00e9al (CRCHUM), Montr\u00e9al, Qu\u00e9bec, Canada"},{"name":"D\u00e9partement de m\u00e9decine, Facult\u00e9 de m\u00e9decine, Universit\u00e9 de Montr\u00e9al, Montr\u00e9al, Qu\u00e9bec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1042\/CS20080532"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0173943"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1111\/hiv.12357"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.2174\/1381612823666170704130635"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12977-018-0397-2"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1318249111"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature16933"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-41788-9"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.3390\/jcm11133579"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.3390\/jcm9072091"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0059302"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1093\/ofid\/ofw097"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11904-012-0147-3"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a007096"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.3390\/v14061325"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10620-018-5215-0"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00773-20"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.723196"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2021.615342"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1093\/ofid\/ofaa115"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00430-018-0538-1"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.726419"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-022-08871-0"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0187095"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiy136"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00609-14"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.20411\/pai.v5i1.348"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2021.103270"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-17898-8"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiw263"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1097\/QAD.0000000000000596"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiaa126"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI171554"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.3350\/cmh.2017.0074"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI75938"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1008151"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.virol.2005.09.063"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.0303093"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1002\/hep4.1074"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI129642"},{"key":"e_1_3_3_42_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiw457"},{"key":"e_1_3_3_43_2","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aap9927"},{"key":"e_1_3_3_44_2","doi-asserted-by":"publisher","DOI":"10.1097\/QAD.0000000000000953"},{"key":"e_1_3_3_45_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1007229"},{"key":"e_1_3_3_46_2","doi-asserted-by":"publisher","DOI":"10.1097\/00002030-200409240-00011"},{"key":"e_1_3_3_47_2","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.134196"},{"key":"e_1_3_3_48_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm.4156"},{"key":"e_1_3_3_49_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-0898-8"},{"key":"e_1_3_3_50_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2015.06.019"}],"container-title":["Journal of Virology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/jvi.01105-23","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/jvi.01105-23","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,12,21]],"date-time":"2023-12-21T09:07:28Z","timestamp":1703149648000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/jvi.01105-23"}},"subtitle":[],"editor":[{"given":"Viviana","family":"Simon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2023,12,21]]},"references-count":49,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2023,12,21]]}},"alternative-id":["10.1128\/jvi.01105-23"],"URL":"https:\/\/doi.org\/10.1128\/jvi.01105-23","relation":{},"ISSN":["0022-538X","1098-5514"],"issn-type":[{"value":"0022-538X","type":"print"},{"value":"1098-5514","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,12,21]]},"assertion":[{"value":"2023-07-20","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-11-16","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-12-05","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e01105-23"}}